当前期刊: The FEBS Journal Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Ring Finger Protein 11 (RNF11) acts on ligand‐activated EGFR via the direct interaction with the UIM region of ANKRD13 protein family
    FEBS J. (IF 4.53) Pub Date : 2020-01-27
    Anna Mattioni; Karsten Boldt; Giulio Auciello; Masayuki Komada; Joshua Z. Rappoport; Marius Ueffing; Luisa Castagnoli; Gianni Cesareni; Elena Santonico

    RNF11 is an evolutionary conserved RING E3‐ligase that is overexpressed in several human tumours. Although several reports have highlighted its involvement in crucial cellular processes, the mechanistic details underlying its function are still poorly understood. Utilizing SILAC‐based proteomics analysis, we identified 51 proteins that co‐immunoprecipitate with wild‐type RNF11 and/or with its catalytically inactive mutant. We focused our attention on the interaction of RNF11 with ANKRD13s family. Members of the ANKRD13 family contain ubiquitin‐interacting motifs (UIM) that recognize the Lys‐63‐linked ubiquitin chains appended to EGFR soon after ligand binding. We show that ANKRD13A, 13B and 13D form a complex with RNF11 in vivo and that the UIMs are required for complex formation. However, at odds with the conventional UIM binding mode, ubiquitin modification of RNF11 is not required for the interaction with ANKRD13 proteins. We also show that the interaction between ANKRD13A and RNF11 is modulated by the EGF stimulus and that a complex formed by ANKRD13A, RNF11 and activated EGFR is transiently assembled in the early phases of receptor endocytosis. Moreover, loss‐of‐function of the E3 ligases ITCH or RNF11 respectively abrogates or increases the ubiquitination of endogenous ANKRD13A, affecting its ability to bind activated EGFR. We propose a model whereby the ANKRD13 proteins act as molecular scaffolds that promote the transient formation of a complex between the activated EGFR and the E3‐ligases ITCH and RNF11. By regulating the ubiquitination status of ANKRD13A and consequently its endocytic adaptor function, RNF11 promotes sorting of the activated EGFR for lysosomal degradation.

    更新日期:2020-01-27
  • Characterization of a bacterial copper‐dependent lytic polysaccharide monooxygenase with an unusual second coordination sphere
    FEBS J. (IF 4.53) Pub Date : 2020-01-24
    Alessia Munzone; Bilal El Kerdi; Mathieu Fanuel; Hélène Rogniaux; David Ropartz; Marius Réglier; Antoine Royant; A. Jalila Simaan; Christophe Decroos
    更新日期:2020-01-26
  • Amyloid protein aggregates: new clients for mitochondrial energy production in the brain?
    FEBS J. (IF 4.53) Pub Date : 2020-01-25
    Senthilkumar Sivanesan; Edwin Chang; Mathew D. Howell; Jayakumar Rajadas

    Mitochondria are key organelles which maintain energy metabolism and cellular homeostasis. Mitochondria support transcriptional regulation and proteostatic signaling mechanisms through crosstalk between the mitochondria itself, the nucleus, and the cytoplasm. Mitochondrial dysfunction leads to impaired proteostasis and both are key pathological features of age‐related neurological disorders. For example, Alzheimer’s and Parkinson’s disease feature mitochondrial‐targeted protein aggregates and impaired mitochondrial function, although the mechanistic causes are poorly understood. Vascular abnormalities and hypometabolism in such neurological diseases are reported several years before key clinical disease symptoms even become apparent. Recent investigations suggest that processing of such aggregates within mitochondria can offer protective functions, specifically by restoring energy (ATP) in starving cells. We hypothesize that the accumulation of protein aggregates in mitochondria can not only disrupt its functions, but also render a protective role to fulfill energy demands in hypometabolic conditions. Growing evidence favors mitochondrial defense to toxic amyloid aggregates/oligomers as a protective response. In this view‐point article, we will present several publications (in addition to our own) that serve to connect the possible role of protein aggregates in mitochondrial energy production for degenerative conditions.

    更新日期:2020-01-26
  • Rutinosidase from Aspergillus niger: crystal structure and insight into the enzymatic activity
    FEBS J. (IF 4.53) Pub Date : 2020-01-24
    Petr Pachl; Jana Kapešová; Jiří Brynda; Lada Biedermannová; Helena Pelantová; Pavla Bojarová; Vladimír Křen; Pavlína Řezáčová; Michael Kotik
    更新日期:2020-01-24
  • Poor old pores—The challenge of making and maintaining nuclear pore complexes in aging
    FEBS J. (IF 4.53) Pub Date : 2020-01-23
    Irina L. Rempel; Anton Steen; Liesbeth M. Veenhoff
    更新日期:2020-01-24
  • Highly drug‐resistant HIV‐1 protease reveals decreased intra‐subunit interactions due to clusters of mutations
    FEBS J. (IF 4.53) Pub Date : 2020-01-23
    Daniel W. Kneller; Johnson Agniswamy; Robert W. Harrison; Irene T. Weber
    更新日期:2020-01-24
  • Energy landscape of domain motion in glutamate dehydrogenase deduced from cryo‐electron microscopy
    FEBS J. (IF 4.53) Pub Date : 2020-01-24
    Mao Oide; Takayuki Kato; Tomotaka Oroguchi; Masayoshi Nakasako

    Analysis of the conformational changes of protein is important to elucidate the mechanisms of protein motions correlating with their function. Here, we studied the spontaneous domain motion of unliganded glutamate dehydrogenase from Thermococcus profundus using cryo‐electron microscopy and proposed a novel method to construct free‐energy landscape of protein conformations. Each subunit of the homo‐hexameric enzyme comprises nucleotide‐binding domain and hexamer‐forming core‐domain. A large active‐site cleft is situated between the two domains and varies from open to close according to the motion of a nucleotide‐binding domain. A three‐dimensional map reconstructed from all cryo‐electron microscopy images displayed disordered volumes of nucleotide‐binding domains, suggesting that nucleotide‐binding domains in the collected images adopted various conformations in domain motion. Focused classifications on nucleotide‐binding domain of subunits provided several maps of possible conformations in domain motion. To deduce what kinds of conformations appeared in EM images, we developed a novel analysis method that describe the EM maps as a linear combination of representative conformations appearing in a 200‐ns molecular dynamics simulation as reference. The analysis enabled us to estimate the appearance frequencies of the representative conformations, which illustrated a free‐energy landscape in domain motion. In the open/close domain motion, two free‐energy basins hindered the direct transformation from open to closed state. Structure models constructed for representative EM maps in classifications demonstrated the correlation between the energy landscape and conformations in domain motion. Based on the results, the domain motion in glutamate dehydrogenase and the analysis method to visualize conformational changes and free‐energy landscape were discussed.

    更新日期:2020-01-24
  • Framing cancer progression: influence of the organ‐ and tumour‐specific matrisome
    FEBS J. (IF 4.53) Pub Date : 2020-01-23
    Maria Rafaeva; Janine T. Erler

    The extracellular matrix (ECM) plays a crucial role in regulating normal organ homeostasis. It provides mechanical and biochemical cues directing cellular behaviour and, therefore, has control over the progression of diseases such as cancer. Recent efforts have greatly enhanced our knowledge of the protein composition of the ECM and its regulators, the so‐called matrisome, in healthy and cancerous tissues, yet an overview of the common signatures and organ‐specific ECM in cancer is missing. Here, we address this by taking a detailed approach to review why cancer grows in certain organs, and focus on the influence of the matrisome at primary and metastatic tumour sites. Our in‐depth and comprehensive review of the current literature and general understanding, identifies important commonalities and distinctions, providing insight into the biology of metastasis which could pave the way to improve future diagnostics and therapies.

    更新日期:2020-01-24
  • CRISPR screening strategies for microRNA target identification
    FEBS J. (IF 4.53) Pub Date : 2020-01-23
    Bing Yang; Katherine McJunkin

    Identifying microRNA (miRNA) target genes remains a major challenge in understanding the roles miRNAs play in gene regulation. Furthermore, understanding which miRNA‐target interactions are the most biologically important is even more difficult. We present CRISPR‐based strategies to identify essential miRNA binding sites. First, CRISPR knockout screens can easily be adapted to identify genes whose inactivation suppresses miRNA mutant phenotypes. Second, a custom approach to target individual miRNA binding sites via CRISPR can identify sites whose mutation recapitulates miRNA mutant phenotypes. We emphasize that the latter approach requires a readout of mutational profile (rather than sgRNA abundance) when applied in a negative selection setting. Overall, the advent of CRISPR technology alongside improving empirical means of miRNA target identification will accelerate our dissection of miRNA gene regulatory networks.

    更新日期:2020-01-24
  • Hypoxia‐inducible factors in metabolic reprogramming during sepsis
    FEBS J. (IF 4.53) Pub Date : 2020-01-23
    Tineke Vanderhaeghen; Jolien Vandewalle; Claude Libert

    Sepsis is a highly heterogeneous syndrome that is caused by an imbalanced host response to infection. Despite huge investments, sepsis remains a contemporary threat with significant burden on health systems. Vascular dysfunction and elevated oxygen consumption by highly metabolically active immune cells result in tissue hypoxia during inflammation. The transcription factor hypoxia‐inducible factor‐1a (HIF1α), and its family members, play an important role in cellular metabolism and adaptation to cellular stress caused by hypoxia. In this review, we discuss the role of HIF in sepsis. We show possible mechanisms by which the inflammatory response activated during sepsis affects the PHD‐HIF system. The activated HIF pathway in turn changes the metabolism of both innate and adaptive immune cells. As HIF expression in leukocytes of septic patients can be directly linked with mortality, we discuss multiple ways of interfering with the HIF signaling pathway.

    更新日期:2020-01-23
  • Sex‐specific perturbation of complex lipids in response to medium‐chain fatty acids in very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD)'
    FEBS J. (IF 4.53) Pub Date : 2020-01-22
    Khaled I. Alatibi; Zeinab Wehbe; Ute Spiekerkoetter; Sara Tucci

    Very‐long‐chain‐acyl‐CoA‐dehydrogenase‐deficiency (VLCAD) is the most common defect of long‐chain fatty acid β‐oxidation. The recommended treatment includes the application of medium‐chain‐triglycerides (MCT). However, long‐term treatment of VLCAD‐/‐ mice resulted in the development of a sex specific metabolic syndrome due to the selective activation of the ERK/mTORc1 signaling in females and ERK/PPARγ pathway in males.

    更新日期:2020-01-23
  • Broad domains of histone H3 lysine 4 trimethylation in transcriptional regulation and disease
    FEBS J. (IF 4.53) Pub Date : 2020-01-22
    Shinae Park; Go Woon Kim; So Hee Kwon; Jung‐Shin Lee

    Histone modifications affect transcription by changing the chromatin structure. In particular, histone H3 lysine 4 trimethylation (H3K4me3) is one of the most recognized epigenetic marks of active transcription. Whilst many studies have provided evidence of the correlation between H3K4me3 and active transcription, details regarding the mechanism involved remain unclear. The first study on the broad H3K4me3 domain was reported in 2014; subsequently, the function of this domain has been studied in various cell types. In this review, we summarized the recent studies on the role of the broad H3K4me3 domain in transcription, development, memory formation, and several diseases, including cancer and autoimmune diseases. The broadest H3K4me3 domains are associated with increased transcriptional precision of cell‐type‐specific genes related to cell identity and other essential functions. The broad H3K4me3 domain regulates maternal zygotic activation in early mammalian development. In systemic autoimmune diseases, high expression of immune‐responsive genes requires the presence of the broad H3K4me3 domain in the promoter‐proximal regions. Transcriptional repression of tumor‐suppressor genes is associated with the shortening of the broad H3K4me3 domains in cancer cells. Additionally, the broad H3K4me3 domain interacts with the super‐enhancer to regulate cancer‐associated genes. During memory formation, H3K4me3 breadth is regulated in the hippocampus CA1 neurons. Taken together, these findings indicate that H3K4me3 breadth is essential for the regulation of the transcriptional output across multiple cell types.

    更新日期:2020-01-23
  • New regulatory mechanism‐based inhibitors of aspartate transcarbamoylase for potential anticancer drug development
    FEBS J. (IF 4.53) Pub Date : 2020-01-22
    Zhen Lei; Biying Wang; Zhifang Lu; Nan Wang; Hongwei Tan; Zheng Jimin; Zongchao Jia

    Aspartate transcarbamoylase (ATCase) is a key enzyme which regulates and catalyzes the second step of de novo pyrimidine synthesis in all organisms. E. coli ATCase is a prototypic enzyme regulated by both product feedback and substrate cooperativity, whereas human ATCase is a potential anticancer target. Through structural and biochemical analyses, we revealed that R167/130's loop region in ATCase serves as a gatekeeper for the active site, playing a new and unappreciated regulatory role in the catalytic cycle of ATCase. Based on virtual compound screening simultaneously targeting the new regulatory region and active site of human ATCase, two compounds were identified to exhibit strong inhibition of ATCase activity, proliferation of multiple cancer cell lines, and growth of xenograft tumors. Our work has not only revealed a previously unknown regulatory region of ATCase that helps uncover the catalytic and regulatory mechanism of ATCase, but also successfully guided the identification of new ATCase inhibitors for anticancer drug development using a dual‐targeting strategy.

    更新日期:2020-01-23
  • Regulation of endo‐lysosomal pathway and autophagic flux by broad‐spectrum antipathogen inhibitor ABMA
    FEBS J. (IF 4.53) Pub Date : 2020-01-21
    Yu Wu; Claire Boulogne; Stefan Carle; Maria Podinovskaia; Holger Barth; Anne Spang; Jean‐Christophe Cintrat; Daniel Gillet; Julien Barbier
    更新日期:2020-01-22
  • 14‐3‐3 protein binding blocks the dimerization interface of caspase‐2
    FEBS J. (IF 4.53) Pub Date : 2020-01-21
    Dana Kalabova; Frantisek Filandr; Miroslava Alblova; Olivia Petrvalska; Matej Horvath; Petr Man; Tomas Obsil; Veronika Obsilova

    Among all species, caspase‐2 (C2) is the most evolutionarily conserved caspase required for effective initiation of apoptosis following death stimuli. C2 is activated through dimerization and autoproteolytic cleavage and inhibited through phosphorylation at Ser139 and Ser164, within the linker between the caspase recruitment and p19 domains of the zymogen, followed by association with the adaptor protein 14‐3‐3, which maintains C2 in its immature form procaspase (proC2). However, the mechanism of 14‐3‐3‐dependent inhibition of C2 activation remains unclear. Here, we report the structural characterization of the complex between proC2 and 14‐3‐3 by hydrogen/deuterium mass spectrometry (HDX‐MS) and protein crystallography to determine the molecular basis for 14‐3‐3‐mediated inhibition of C2 activation. Our data reveal that the 14‐3‐3 dimer interacts with proC2 not only through ligand‐binding grooves but also through other regions outside the central channel, thus explaining the isoform‐dependent specificity of 14‐3‐3 protein binding to proC2 and the substantially higher binding affinity of 14‐3‐3 protein to proC2 than to the doubly phosphorylated peptide. The formation of the complex between 14‐3‐3 protein and proC2 does not induce any large conformational change in proC2. Furthermore, 14‐3‐3 protein interacts with and masks both the nuclear localization sequence (NLS) and the C‐terminal region of the p12 domain of proC2 through transient interactions in which both the p19 and p12 domains of proC2 are not firmly docked onto the surface of 14‐3‐3. This masked region of p12 domain is involved in caspase‐2 dimerization. Therefore, 14‐3‐3 protein likely inhibits proC2 activation by blocking its dimerization surface.

    更新日期:2020-01-22
  • 更新日期:2020-01-21
  • Angiotensin receptor subtypes regulate adipose tissue renewal and remodelling
    FEBS J. (IF 4.53) Pub Date : 2020-01-20
    Pyotr A. Tyurin‐Kuzmin; Natalia I. Kalinina; Konstantin Y. Kulebyakin; Alexander V. Balatskiy; Veronika Y. Sysoeva; Vsevolod A. Tkachuk
    更新日期:2020-01-21
  • Conformational flexibility of GRASPs and their constituent PDZ subdomains reveals structural basis of their promiscuous interactome
    FEBS J. (IF 4.53) Pub Date : 2020-01-20
    Luis Felipe S. Mendes; Mariana R. B. Batista; Peter J. Judge; Anthony Watts; Christina Redfield; Antonio J. Costa‐Filho
    更新日期:2020-01-21
  • Conditional loss of geranylgeranyl diphosphate synthase alleviates acute obstructive cholestatic liver injury by regulating hepatic bile acid metabolism
    FEBS J. (IF 4.53) Pub Date : 2020-01-20
    Wen‐Jun Jia; Qiao‐Li Tang; Shan Jiang; Shi‐Quan Sun; Bin Xue; Yu‐Dong Qiu; Chao‐Jun Li; Liang Mao
    更新日期:2020-01-21
  • The structure of Plasmodium falciparum hydroxymethyldihydropterin pyrophosphokinase‐dihydropteroate synthase reveals the basis of sulfa resistance
    FEBS J. (IF 4.53) Pub Date : 2020-01-19
    Penchit Chitnumsub; Aritsara Jaruwat; Yuwadee Talawanich; Krittikar Noytanom; Benjamas Liwnaree; Sinothai Poen; Yongyuth Yuthavong
    更新日期:2020-01-21
  • USP15 potentiates NF‐κB activation by differentially stabilizing TAB2 and TAB3
    FEBS J. (IF 4.53) Pub Date : 2020-01-19
    Qiaoqiao Zhou; Cheng Cheng; Yujuan Wei; Jing Yang; Wanzhu Zhou; Qiuyi Song; Mengxiang Ke; Wanyao Yan; Ling Zheng; Yu Zhang; Kun Huang
    更新日期:2020-01-21
  • TL1A/TNFR2‐mediated mitochondrial dysfunction of fibroblast‐like synoviocytes increases inflammatory response in patients with rheumatoid arthritis via reactive oxygen species generation
    FEBS J. (IF 4.53) Pub Date : 2020-01-17
    Mahmoud Al‐Azab; Eskandar Qaed; Xunli Ouyang; Abdalkhalig Elkhider; Williams Walana; Han Li; Weiping Li; Yawei Tang; Salah Adlat; Jing Wei; Bing Wang; Xia Li
    更新日期:2020-01-21
  • Tetraspanin 33 (TSPAN33) Regulates Endocytosis and Migration of Human B Lymphocytes by Affecting the Tension of the Plasma Membrane
    FEBS J. (IF 4.53) Pub Date : 2020-01-20
    IC Navarro‐Hernandez; O López‐Ortega; E Acevedo‐Ochoa; R Cervantes‐Díaz; S Romero‐Ramírez; VA Sosa‐Hernandez; DE Meza‐Sánchez; G Juárez‐Vega; CA Pérez‐Martínez; B Chávez‐Munguía; A Galván‐Hernández; A Antillón; I Ortega‐Blake; L Santos‐Argumedo; JM Hernández‐Hernández; JL Maravillas‐Montero

    B lymphocytes are a leukocyte subset capable of developing several functions apart from differentiating into antibody‐secreting cells. These processes are triggered by external activation signals that induce changes in the plasma membrane properties, regulated by the formation of different lipid‐bilayer subdomains that are associated with the underlying cytoskeleton through different linker molecules, thus allowing the functional specialization of regions within the membrane. Among these, there are tetraspanin‐enriched domains. Tetraspanins constitute a superfamily of transmembrane proteins that establish lateral associations with other molecules, determining its activity and localization. In this study, we identified TSPAN33 as an active player during B lymphocyte cytoskeleton and plasma membrane‐related phenomena, including protrusions formation, adhesion, phagocytosis and cell motility. By using an overexpression model of TSPAN33 in human Raji cells, we detected a specific distribution of this protein that includes membrane microvilli, the Golgi apparatus, and extracellular vesicles. Additionally, we identified diminished phagocytic ability and altered cell adhesion properties due to the aberrant expression of integrins. Accordingly, these cells presented an enhanced migratory phenotype, as shown by its augmented chemotaxis and invasion rates. When we evaluated the mechanic response of cells during fibronectin‐induced spreading, we found that TSPAN33 expression inhibited changes in roughness and membrane tension. Contrariwise, TSPAN33 knockdown cells displayed opposite phenotypes to those observed in the overexpression model. Altogether, our data indicate that TSPAN33 represents a regulatory element of the adhesion and migration of B lymphocytes, suggesting a novel implication of this tetraspanin in the control of the mechanical properties of their plasma membrane.

    更新日期:2020-01-21
  • The mutual interplay of gut microbiota, diet and human disease
    FEBS J. (IF 4.53) Pub Date : 2020-01-19
    Placido Illiano; Roberta Brambilla; Cinzia Parolini

    The intestinal milieu harbours the gut microbiota, consisting of a complex community of bacteria, archaea, fungi, viruses, and protozoans that bring to the host organism an endowment of cells and genes more numerous than its own. In the last ten years, mounting evidence has highlighted the prominent influence of the gut mutualistic bacterial communities on human health. Microbial colonization occurs alongside with immune system development and plays a role in intestinal physiology. The community of the gut microbiota does not undergo significant fluctuations throughout adult life. However, bacterial infections, antibiotic treatment, lifestyle, surgery, and diet might profoundly affect it. Gut microbiota dysbiosis, defined as marked alterations in the amount and function of the intestinal microorganisms, is correlated with the aetiology of chronic non‐communicable diseases, ranging from cardiovascular, neurologic, respiratory, and metabolic illnesses to cancer. In this review, we focus on the interplay among gut microbiota, diet, and host to provide a perspective on the role of microbiota and their unique metabolites in the pathogenesis and/or progression of various human disorders. We discuss interventions based on microbiome studies, i.e. faecal microbiota transplantation, probiotics, and prebiotics, to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach toward disease treatment.

    更新日期:2020-01-21
  • The re‐emerging pathophysiological role of the cystathionine‐β‐synthase ‐ hydrogen sulfide system in Down syndrome
    FEBS J. (IF 4.53) Pub Date : 2020-01-19
    Csaba Szabo

    Down syndrome (DS) is associated with significant perturbances in many morphological and biochemical features. Cystathionine‐β‐synthase (CBS) is one of the key mammalian enzymes that is responsible for the biological production of the gaseous transmitter hydrogen sulfide (H2S). When H2S is overproduced, it can exert detrimental cellular effects, in part due to inhibition of mitochondrial Complex IV activity. An increased expression of CBS and the consequent overproduction of H2S is well documented in individuals with DS. Two decades ago, it has been proposed that a toxic overproduction of H2S importantly contributes to the metabolic and neurological deficits associated with DS. However, until recently, this hypothesis has not yet been tested experimentally. Recent data generated in human dermal fibroblasts show that DS cells overproduce H2S, which, in turn, suppresses mitochondrial Complex IV activity and impairs mitochondrial oxygen consumption and ATP generation. Therapeutic CBS inhibition lifts the tonic (and reversible) suppression of Complex IV: this results in the normalization of mitochondrial function in DS cells. H2S may also contribute to the cellular dysfunction via several other molecular mechanisms through interactions with various mitochondrial and extramitochondrial molecular targets. The current article provides a historical background of the field, summarizes the recently published data and their potential implications and outlines potential translational approaches (such as CBS inhibition and H2S neutralization) and future experimental studies in this re‐emerging field of pathobiochemistry.

    更新日期:2020-01-21
  • Issue Information
    FEBS J. (IF 4.53) Pub Date : 2020-01-20
    更新日期:2020-01-21
  • Phosphoinositides in autophagy: current roles and future insights
    FEBS J. (IF 4.53) Pub Date : 2019-11-21
    Lavinia Palamiuc; Archna Ravi; Brooke M. Emerling
    更新日期:2020-01-21
  • 更新日期:2020-01-21
  • 更新日期:2020-01-21
  • Dynamic architectural interplay between leucocytes and mammary epithelial cells
    FEBS J. (IF 4.53) Pub Date : 2019-11-29
    Jessica R. Hitchcock; Katherine Hughes; Olivia B. Harris; Christine J. Watson
    更新日期:2020-01-21
  • PynA is a pyrimidine 5′‐nucleotidase that functions as an antimutator protein in Streptococcus pneumoniae
    FEBS J. (IF 4.53) Pub Date : 2019-09-04
    Aleš Ulrych; Denisa Petráčková; Jana Goldová; Karolína Buriánková; Linda Doubravová; Pavel Branny
    更新日期:2020-01-21
  • Proximity channeling during cyanobacterial phycoerythrobilin synthesis
    FEBS J. (IF 4.53) Pub Date : 2019-07-26
    Marco Aras; Volker Hartmann; Jana Hartmann; Marc M. Nowaczyk; Nicole Frankenberg‐Dinkel
    更新日期:2020-01-21
  • A unique ferrous iron binding mode is associated with large conformational changes for the transport protein FpvC of Pseudomonas aeruginosa
    FEBS J. (IF 4.53) Pub Date : 2019-07-26
    Armelle Vigouroux; Magali Aumont‐Nicaise; Alain Boussac; Loïc Marty; Léa Lo Bello; Pierre Legrand; Karl Brillet; Isabelle J. Schalk; Solange Moréra
    更新日期:2020-01-21
  • Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF3 ubiquitination through recruiting OTUB1
    FEBS J. (IF 4.53) Pub Date : 2019-08-13
    Mengying Xie; Yue Yin; Liqian Chen; Aiping Yin; Yan Liu; Yunzhi Liu; Lijun Dong; Qintao Lai; Jia Zhou; Liyun Zhang; Min Xu; Zhengliang Chen; Daming Zuo
    更新日期:2020-01-21
  • APEX2‐mediated proximity labeling resolves protein networks in Saccharomyces cerevisiae cells
    FEBS J. (IF 4.53) Pub Date : 2019-08-12
    Birgit Singer‐Krüger; Theresa Fröhlich; Mirita Franz‐Wachtel; Nicolas Nalpas; Boris Macek; Ralf‐Peter Jansen
    更新日期:2020-01-21
  • Ubiquitin release from eL40 is required for cytoplasmic maturation and function of 60S ribosomal subunits in Saccharomyces cerevisiae
    FEBS J. (IF 4.53) Pub Date : 2019-07-25
    Sara Martín‐Villanueva; Antonio Fernández‐Pevida; José Fernández‐Fernández; Dieter Kressler; Jesús de la Cruz
    更新日期:2020-01-21
  • NMR and crystallographic structural studies of the extremely stable monomeric variant of human cystatin C with single amino acid substitution
    FEBS J. (IF 4.53) Pub Date : 2019-08-01
    Martyna Maszota‐Zieleniak; Przemyslaw Jurczak; Marta Orlikowska; Igor Zhukov; Dominika Borek; Zbyszek Otwinowski; Piotr Skowron; Zuzanna Pietralik; Maciej Kozak; Aneta Szymańska; Sylwia Rodziewicz‐Motowidło
    更新日期:2020-01-21
  • Complex genetic interactions between DNA polymerase β and the NHEJ ligase
    FEBS J. (IF 4.53) Pub Date : 2019-07-29
    Aya Kurosawa; Hiroyuki Kuboshima; Noritaka Adachi
    更新日期:2020-01-21
  • Identification of two dihydrodipicolinate synthase isoforms from Pseudomonas aeruginosa that differ in allosteric regulation
    FEBS J. (IF 4.53) Pub Date : 2019-08-05
    Rachael E. Impey; Santosh Panjikar; Cody J. Hall; Lucy J. Bock; J. Mark Sutton; Matthew A. Perugini; Tatiana P. Soares da Costa
    更新日期:2020-01-21
  • Proprotein Convertase 7 (PCSK7) Reduces apoA‐V Levels
    FEBS J. (IF 4.53) Pub Date : 2020-01-16
    Yahya Ashraf; Stéphanie Duval; Vatsal Sachan; Rachid Essalmani; Delia Susan‐Resiga; Anna Roubtsova; Josée Hamelin; Stefan Gerhardy; Daniel Kirchhofer; Vincent S. Tagliabracci; Annik Prat; Robert Scott Kiss; Nabil G. Seidah

    The locus of the human proprotein convertase subtilisin‐kexin type‐7 (PC7) gene (PCSK7) is on chromosome 11q23.3 close to the gene‐cluster APOA5/APOA4/APOC3/APOA1, a region implicated in the regulation of lipoprotein metabolism. A GWAS reported the association of PCSK7 SNPs with plasma triglycerides (TG), and exome sequencing of African‐Americans revealed the association of a low‐frequency coding variant of PC7 (R504H; SNP rs142953140) with a ~30% TG‐reduction. Another PCSK7 SNP rs508487 is in linkage disequilibrium with a promoter‐variant of the liver‐derived apolipoprotein A‐V (apoA‐V), an indirect activator of the lipoprotein lipase (LpL), and is associated with elevated TG‐levels. We thus hypothesized that PC7 regulates the levels/activity of apoA‐V. Studies in the human hepatic cell line HuH7 revealed that wild‐type (WT) PC7 and its endoplasmic reticulum (ER)‐retained forms bind to and enhance the degradation of human apoA‐V in acidic lysosomes in a non‐enzymatic fashion. PC7‐induced degradation of apoA‐V is inhibited by bafilomycin‐A1, and the alkalinizing agents: chloroquine and NH4Cl. Thus, the PC7‐induced apoA‐V degradation implicates an ER‐lysosomal communication inhibited by bafilomycin‐A1. In vitro, the natural R504H mutant enhances PC7 Ser505‐phosphorylation at the structurally‐exposed Ser‐X‐Glu507 motif recognized by the secretory kinase Fam20C. Co‐expression of the phosphomimetic PC7‐S505E with apoA‐V resulted in lower degradation compared to WT, suggesting that Ser505 phosphorylation of PC7 lowers TG levels via reduced apoA‐V degradation. In agreement, in Pcsk7‐/‐ mice fed high‐fat diet, plasma apoA‐V levels and adipocyte LpL activity are increased, providing an in vivo mechanistic link for a role of liver PC7 in enhanced TG storage in adipocytes.

    更新日期:2020-01-17
  • C.elegans phosphatase complexes in UniProtKB and Complex Portal
    FEBS J. (IF 4.53) Pub Date : 2020-01-16
    Hema Bye‐A‐Jee; Rossana Zaru; Michele Magrane; Sandra Orchard;

    Phosphatases play an essential role in the regulation of protein phosphorylation. Less abundant than kinases, many phosphatases are components of one or more macromolecular complexes with different substrate specificities and specific functionalities. The expert scientific curation of phosphatase complexes for the UniProt and Complex Portal databases supports the whole scientific community by collating and organising small‐ and large‐scale experimental data from the scientific literature into context‐specific central resources, where the data can be freely accessed and used to further academic and translational research. In this review, we discuss how the diverse biological functions of phosphatase complexes are presented in UniProt and the Complex Portal, and how understanding the biological significance of phosphatase complexes in C.elegans offers insight into the mechanisms of substrate diversity in a variety of cellular and molecular processes.

    更新日期:2020-01-16
  • Mitochondrial reactive oxygen species‐mediated cytotoxicity of intracellularly accumulated dihydrosphingosine in the yeast Saccharomyces cerevisiae
    FEBS J. (IF 4.53) Pub Date : 2020-01-15
    Nobuaki Arita; Risa Sakamoto; Motohiro Tani

    In eukaryotic cells, the content of sphingoid long‐chain bases (LCBs) is generally much lower than that of complex sphingolipids and ceramides, and the quantitative balance of these metabolites in cells is tightly regulated. In the budding yeast Saccharomyces cerevisiae, it has been demonstrated that exogenously added phytosphingosine (PHS) causes a strong growth defect in tryptophan‐auxotrophic cells, due to delayed uptake of tryptophan from the culture medium; however, the growth inhibitory effect of dihydrosphingosine (DHS) is less than that of PHS in tryptophan‐auxotrophic cells. Here, we found that, in tryptophan‐prototrophic yeast cells, exogenously added DHS is much more toxic than PHS. Exogenously added DHS is converted to PHS, Cers or LCB 1‐phosphates through the action of sphingolipid C4‐hydroxylase, Cer synthases or LCB kinases, respectively; however, suppression of further metabolism of DHS in cells resulted in an increase in the growth inhibitory activity of exogenously added DHS, indicating that DHS itself is causative of the cytotoxicity. The cytotoxicity of DHS was not mediated by Pkh1/2, Sch9, and Ypk1/2 kinases, intracellular targets of LCBs. DHS treatment caused an increase in mitochondria‐derived reactive oxygen species, and the cytotoxic effect of DHS was suppressed by depletion of mitochondrial DNA or antioxidant N‐acetylcysteine, but enhanced by deletion of SOD1 and SOD2 encoding superoxide dismutases. Thus, collectively, these results indicated that intracellularly accumulated DHS has mitochondrial reactive oxygen species‐mediated cytotoxic activity, which is much more potent than that of PHS.

    更新日期:2020-01-16
  • Glycan biomarkers for Alzheimer disease correlate with T‐tau and P‐tau in cerebrospinal fluid in subjective cognitive impairment
    FEBS J. (IF 4.53) Pub Date : 2020-01-14
    Sophia Schedin‐Weiss; Stefan Gaunitz; Ping Sui; Qiushi Chen; Stuart M. Haslam; Kaj Blennow; Bengt Winblad; Anne Dell; Lars O. Tjernberg
    更新日期:2020-01-14
  • Cyclic nucleotides, gut physiology and inflammation
    FEBS J. (IF 4.53) Pub Date : 2020-01-14
    Hari Prasad; Avinash Ravindranath Shenoy; Sandhya Srikant Visweswariah
    更新日期:2020-01-14
  • Targeting proline in (phospho)proteomics
    FEBS J. (IF 4.53) Pub Date : 2020-01-13
    Saar A. M. van der Laarse; Charlotte A. G. H. van Gelder; Marshall Bern; Michiel Akeroyd; Maurien M. A. Olsthoorn; Albert J. R. Heck
    更新日期:2020-01-14
  • A Na+ A1AO ATP synthase with a V‐type c subunit in a mesophilic bacterium
    FEBS J. (IF 4.53) Pub Date : 2020-01-13
    Dennis Litty; Volker Müller
    更新日期:2020-01-14
  • Nitrogen storage regulation by PII protein: lessons learned from taxonomic outliers
    FEBS J. (IF 4.53) Pub Date : 2020-01-13
    Vicente Rubio; Clara Marco‐Marín; José Luis Llácer
    更新日期:2020-01-14
  • Development of an in vitro screening assay for PIP5K1α lipid kinase and identification of potent inhibitors
    FEBS J. (IF 4.53) Pub Date : 2020-01-13
    Katja Strätker; Samer Haidar; Ángel Amesty; Ehab El‐Awaad; Claudia Götz; Ana Estévez‐Braun; Joachim Jose
    更新日期:2020-01-14
  • Deciphering the molecular mechanism of FLT3 resistance mutations
    FEBS J. (IF 4.53) Pub Date : 2020-01-14
    Panagiota S. Georgoulia; Sinisa Bjelic; Ran Friedman

    FMS‐like tyrosine kinase 3 (FLT3) has been found to be mutated in ~30% of acute myeloid leukaemia (AML) patients. Small‐molecule inhibitors targeting FLT3 that are currently approved or still undergoing clinical trials, are subject to drug resistance due to FLT3 mutations. How these mutations lead to drug resistance is hitherto poorly understood. Herein, we studied the molecular mechanism of the drug resistance mutations D835N, Y842S and M664I which confer resistance against the most advanced inhibitors, quizartinib and PLX3397 (pexidartinib), using enzyme kinetics and computer simulations. In vitro kinase assays were performed to measure the comparative catalytic activity of the native protein and the mutants, using a bacterial expression system developed to this aim. Our results reveal that the differential drug sensitivity profiles can be rationalised by the dynamics of the protein‐drug interactions and perturbation of the intra‐protein contacts upon mutations. Drug binding induced a single conformation in the native protein, whereas multiple conformations were observed otherwise (in the mutants or in the absence of drugs). The end‐point kinetics measurements indicated that the three resistant mutants conferred catalytic activity that is at least as high as that of the reference without such mutations. Overall, our calculations and measurements suggest that the structural dynamics of the drug resistant mutants that affect the active state, and the increased conformational freedom of the remaining inactive drug‐bound population are the two major factors that contribute to drug resistance in FLT3 harbouring cancer cells. Our results explain the mechanism of drug resistance mutations and can aid to the design of more effective tyrosine kinase inhibitors.

    更新日期:2020-01-14
  • Evolution‐guided engineering of non‐heme iron enzymes involved in nogalamycin biosynthesis
    FEBS J. (IF 4.53) Pub Date : 2020-01-12
    Benjamin Nji Wandi; Vilja Siitonen; Pedro Dinis; Vladimir Vukic; Tiina A. Salminen; Mikko Metsä‐Ketelä
    更新日期:2020-01-13
  • Genome‐wide mRNA profiling identifies RCAN1 and GADD45A as regulators of the transitional switch from survival to apoptosis during ER stress
    FEBS J. (IF 4.53) Pub Date : 2020-01-10
    Rafal Bartoszewski; Magdalena Gebert; Anna Janaszak‐Jasiecka; Aleksandra Cabaj; Jarosław Króliczewski; Sylwia Bartoszewska; Aleksandra Sobolewska; David K. Crossman; Renata Ochocka; Wojciech Kamysz; Leszek Kalinowski; Michał Dąbrowski; James F. Collawn
    更新日期:2020-01-13
  • How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation
    FEBS J. (IF 4.53) Pub Date : 2020-01-10
    Margaret E. Glasner; Dat P. Truong; Benjamin C. Morse
    更新日期:2020-01-10
  • Annexin A6 improves anti‐migratory and anti‐invasive properties of tyrosine kinase inhibitors in EGFR overexpressing human squamous epithelial cells
    FEBS J. (IF 4.53) Pub Date : 2020-01-09
    Monira Hoque; Yasmin A. Elmaghrabi; Meryem Köse; Syed S. Beevi; Jaimy Jose; Elsa Meneses‐Salas; Patricia Blanco‐Muñoz; James R. W. Conway; Alexander Swarbrick; Paul Timpson; Francesc Tebar; Carlos Enrich; Carles Rentero; Thomas Grewal
    更新日期:2020-01-10
  • Verteporfin inhibits oxidative phosphorylation and induces cell death specifically in glioma stem cells
    FEBS J. (IF 4.53) Pub Date : 2020-01-09
    Kenta Kuramoto; Masahiro Yamamoto; Shuhei Suzuki; Tomomi Sanomachi; Keita Togashi; Shizuka Seino; Chifumi Kitanaka; Masashi Okada
    更新日期:2020-01-09
  • Low copper availability limits Helicobacter infection in mice
    FEBS J. (IF 4.53) Pub Date : 2020-01-08
    Roberta Esposito; Megi Vllahu; Silvana Morello; Daniela Baldantoni; Alessandro Bellino; Antonello Petrella; Daniela Eletto; Amalia Porta; Alessandra Tosco
    更新日期:2020-01-09
  • BAX inhibitor‐1: between stress and survival
    FEBS J. (IF 4.53) Pub Date : 2020-01-08
    Cynthia Lebeaupin; Marina Blanc; Déborah Vallée; Harald Keller; Béatrice Bailly‐Maitre
    更新日期:2020-01-08
  • Kinetic and structural studies of Trypanosoma and Leishmania phosphofructokinases show evolutionary divergence and identify AMP as a switch regulating glycolysis versus gluconeogenesis
    FEBS J. (IF 4.53) Pub Date : 2020-01-08
    Peter M. Fernandes; James Kinkead; Iain W. McNae; Monserrat Vásquez‐Valdivieso; Martin A. Wear; Paul A. M. Michels; Malcolm D. Walkinshaw
    更新日期:2020-01-08
  • Structural features of the diatom photosystem II–light‐harvesting antenna complex
    FEBS J. (IF 4.53) Pub Date : 2020-01-07
    Wenda Wang; Songhao Zhao; Xiong Pi; Tingyun Kuang; Sen‐Fang Sui; Jian‐Ren Shen
    更新日期:2020-01-08
  • Regulation of CHK1 by the Ubiquitin–Proteasome System
    FEBS J. (IF 4.53) Pub Date : 2020-01-06
    Maëlle Cartel; Christine Didier
    更新日期:2020-01-06
  • Issue Information
    FEBS J. (IF 4.53) Pub Date : 2020-01-06
    更新日期:2020-01-06
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
加州大学洛杉矶分校
上海纽约大学William Glover
南开大学化学院周其林
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug