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Unveiling the Intricate Connection: Cell Volume as a Key Regulator of Mechanotransduction Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-03-01 Jing Xie, Wilhelm T.S. Huck, Min Bao
The volumes of living cells undergo dynamic changes to maintain the cells’ structural and functional integrity in many physiological processes. Minor fluctuations in cell volume can serve as intrinsic signals that play a crucial role in cell fate determination during mechanotransduction. In this review, we discuss the variability of cell volume and its role in vivo, along with an overview of the mechanisms
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Single-Cell Mechanics: Structural Determinants and Functional Relevance Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-21 Marta Urbanska, Jochen Guck
The mechanical phenotype of a cell determines its ability to deform under force and is therefore relevant to cellular functions that require changes in cell shape, such as migration or circulation through the microvasculature. On the practical level, the mechanical phenotype can be used as a global readout of the cell's functional state, a marker for disease diagnostics, or an input for tissue modeling
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Biophysical Modeling of Synaptic Plasticity Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-21 Christopher T. Lee, Miriam Bell, Mayte Bonilla-Quintana, Padmini Rangamani
Dendritic spines are small, bulbous compartments that function as postsynaptic sites and undergo intense biochemical and biophysical activity. The role of the myriad signaling pathways that are implicated in synaptic plasticity is well studied. A recent abundance of quantitative experimental data has made the events associated with synaptic plasticity amenable to quantitative biophysical modeling.
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Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-21 George A. Pantelopulos, Conor B. Abraham, John E. Straub
Cholesterol has been conjectured to be a modulator of the amyloid cascade, the mechanism that produces the amyloid-β (Aβ) peptides implicated in the onset of Alzheimer's disease. We propose that cholesterol impacts the genesis of Aβ not through direct interaction with proteins in the bilayer, but indirectly by inducing the liquid-ordered phase and accompanying liquid–liquid phase separations, which
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Bacterial Electrophysiology Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-21 Wei-Chang Lo, Ekaterina Krasnopeeva, Teuta Pilizota
Bacterial ion fluxes are involved in the generation of energy, transport, and motility. As such, bacterial electrophysiology is fundamentally important for the bacterial life cycle, but it is often neglected and consequently, by and large, not understood. Arguably, the two main reasons for this are the complexity of measuring relevant variables in small cells with a cell envelope that contains the
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Biomolecular Condensates in Contact with Membranes Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-16 Agustín Mangiarotti, Rumiana Dimova
Biomolecular condensates are highly versatile membraneless organelles involved in a plethora of cellular processes. Recent years have witnessed growing evidence of the interaction of these droplets with membrane-bound cellular structures. Condensates’ adhesion to membranes can cause their mutual molding and regulation, and their interaction is of fundamental relevance to intracellular organization
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From Nucleosomes to Compartments: Physicochemical Interactions Underlying Chromatin Organization Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-12 Shuming Liu, Advait Athreya, Zhuohan Lao, Bin Zhang
Chromatin organization plays a critical role in cellular function by regulating access to genetic information. However, understanding chromatin folding is challenging due to its complex, multiscale nature. Significant progress has been made in studying in vitro systems, uncovering the structure of individual nucleosomes and their arrays, and elucidating the role of physicochemical forces in stabilizing
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Next-Generation Genetically Encoded Fluorescent Biosensors Illuminate Cell Signaling and Metabolism Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-12 Michelle S. Frei, Sohum Mehta, Jin Zhang
Genetically encoded fluorescent biosensors have revolutionized the study of cell signaling and metabolism, as they allow for live-cell measurements with high spatiotemporal resolution. This success has spurred the development of tailor-made biosensors that enable the study of dynamic phenomena on different timescales and length scales. In this review, we discuss different approaches to enhancing and
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Emergent Spatiotemporal Organization in Stochastic Intracellular Transport Dynamics Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-12 Kunaal Joshi, Harrison M. York, Charles S. Wright, Rudro R. Biswas, Senthil Arumugam, Srividya Iyer-Biswas
The interior of a living cell is an active, fluctuating, and crowded environment, yet it maintains a high level of coherent organization. This dichotomy is readily apparent in the intracellular transport system of the cell. Membrane-bound compartments called endosomes play a key role in carrying cargo, in conjunction with myriad components including cargo adaptor proteins, membrane sculptors, motor
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NMR and Single-Molecule FRET Insights into Fast Protein Motions and Their Relation to Function Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-02-12 Paul Schanda, Gilad Haran
Proteins often undergo large-scale conformational transitions, in which secondary and tertiary structure elements (loops, helices, and domains) change their structures or their positions with respect to each other. Simple considerations suggest that such dynamics should be relatively fast, but the functional cycles of many proteins are often relatively slow. Sophisticated experimental methods are starting
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When Force Met Fluorescence: Single-Molecule Manipulation and Visualization of Protein–DNA Interactions Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-01-18 Gabriella N.L. Chua, Shixin Liu
Myriad DNA-binding proteins undergo dynamic assembly, translocation, and conformational changes while on DNA or alter the physical configuration of the DNA substrate to control its metabolism. It is now possible to directly observe these activities—often central to the protein function—thanks to the advent of single-molecule fluorescence- and force-based techniques. In particular, the integration of
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Mitochondrial Dynamics at Different Levels: From Cristae Dynamics to Interorganellar Cross Talk Annu. Rev. Biophys. (IF 12.4) Pub Date : 2024-01-02 Arun Kumar Kondadi, Andreas S. Reichert
Mitochondria are essential organelles performing important cellular functions ranging from bioenergetics and metabolism to apoptotic signaling and immune responses. They are highly dynamic at different structural and functional levels. Mitochondria have been shown to constantly undergo fusion and fission processes and dynamically interact with other organelles such as the endoplasmic reticulum, peroxisomes
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Translation Dynamics of Single mRNAs in Live Cells Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-12-22 Tatsuya Morisaki, O'Neil Wiggan, Timothy J. Stasevich
The translation of messenger RNA (mRNA) into proteins represents the culmination of gene expression. Recent technological advances have revolutionized our ability to investigate this process with unprecedented precision, enabling the study of translation at the single-molecule level in real time within live cells. In this review, we provide an overview of single-mRNA translation reporters. We focus
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The Effects of Codon Usage on Protein Structure and Folding Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-12-22 McKenze J. Moss, Laura M. Chamness, Patricia L. Clark
The rate of protein synthesis is slower than many folding reactions and varies depending on the synonymous codons encoding the protein sequence. Synonymous codon substitutions thus have the potential to regulate cotranslational protein folding mechanisms, and a growing number of proteins have been identified with folding mechanisms sensitive to codon usage. Typically, these proteins have complex folding
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Ancestral Reconstruction and the Evolution of Protein Energy Landscapes Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-12-22 Lauren O. Chisholm, Kona N. Orlandi, Sophia R. Phillips, Michael J. Shavlik, Michael J. Harms
A protein's sequence determines its conformational energy landscape. This, in turn, determines the protein's function. Understanding the evolution of new protein functions therefore requires understanding how mutations alter the protein energy landscape. Ancestral sequence reconstruction (ASR) has proven a valuable tool for tackling this problem. In ASR, one phylogenetically infers the sequences of
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Metabolomics and Microbial Metabolism: Toward a Systematic Understanding Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-12-18 Duncan Holbrook-Smith, Julian Trouillon, Uwe Sauer
Over the past decades, our understanding of microbial metabolism has increased dramatically. Metabolomics, a family of techniques that are used to measure the quantities of small molecules in biological samples, has been central to these efforts. Advances in analytical chemistry have made it possible to measure the relative and absolute concentrations of more and more compounds with increasing levels
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High-Speed Atomic Force Microscopy for Filming Protein Molecules in Dynamic Action Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-12-07 Toshio Ando, Shingo Fukuda, Kien X. Ngo, Holger Flechsig
Structural biology is currently undergoing a transformation into dynamic structural biology, which reveals the dynamic structure of proteins during their functional activity to better elucidate how they function. Among the various approaches in dynamic structural biology, high-speed atomic force microscopy (HS-AFM) is unique in the ability to film individual molecules in dynamic action, although only
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Biophysical Principles Emerging from Experiments on Protein–Protein Association and Aggregation Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-10-31 Barbara Hribar-Lee, Miha Lukšič
Protein–protein association and aggregation are fundamental processes that play critical roles in various biological phenomena, from cellular signaling to disease progression. Understanding the underlying biophysical principles governing these processes is crucial for elucidating their mechanisms and developing strategies for therapeutic intervention. In this review, we provide an overview of recent
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Next-Gen Biophysics: Look to the Forest, Beyond the Trees. Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Jeremy Schmit,Ken A Dill
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Prospects and Limitations of High-Resolution Single-Particle Cryo-Electron Microscopy Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Ashwin Chari, Holger Stark
Single particle cryo-electron microscopy (cryo-EM) has matured into a robust method for the determination of biological macromolecule structures in the past decade, complementing X-ray crystallography and nuclear magnetic resonance. Constant methodological improvements in both cryo-EM hardware and image processing software continue to contribute to an exponential growth in the number of structures
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Mechanisms of Protein Quality Control in the Endoplasmic Reticulum by a Coordinated Hsp40-Hsp70-Hsp90 System Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Judy L.M. Kotler, Timothy O. Street
The Hsp40, Hsp70, and Hsp90 chaperone families are ancient, highly conserved, and critical to cellular protein homeostasis. Hsp40 chaperones can transfer their protein clients to Hsp70, and Hsp70 can transfer clients to Hsp90, but the functional benefits of these transfers are unclear. Recent structural and mechanistic work has opened up the possibility of uncovering how Hsp40, Hsp70, and Hsp90 work
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Mitochondrial Ion Channels Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Ildiko Szabo, Adam Szewczyk
Mitochondria are involved in multiple cellular tasks, such as ATP synthesis, metabolism, metabolite and ion transport, regulation of apoptosis, inflammation, signaling, and inheritance of mitochondrial DNA. The majority of the correct functioning of mitochondria is based on the large electrochemical proton gradient, whose component, the inner mitochondrial membrane potential, is strictly controlled
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Mechanism of Activation of the Visual Receptor Rhodopsin Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Steven O. Smith
Rhodopsin is the photoreceptor in human rod cells responsible for dim-light vision. The visual receptors are part of the large superfamily of G protein–coupled receptors (GPCRs) that mediate signal transduction in response to diverse diffusible ligands. The high level of sequence conservation within the transmembrane helices of the visual receptors and the family A GPCRs has long been considered evidence
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The Expanded Central Dogma: Genome Resynthesis, Orthogonal Biosystems, Synthetic Genetics Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Karola Gerecht, Niklas Freund, Wei Liu, Yang Liu, Maximilian J.L.J. Fürst, Philipp Holliger
Synthetic biology seeks to probe fundamental aspects of biological form and function by construction [i.e., (re)synthesis] rather than deconstruction (analysis). In this sense, biological sciences now follow the lead given by the chemical sciences. Synthesis can complement analytic studies but also allows novel approaches to answering fundamental biological questions and opens up vast opportunities
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Decoding and Recoding of mRNA Sequences by the Ribosome Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Marina V. Rodnina
Faithful translation of messenger RNA (mRNA) into protein is essential to maintain protein homeostasis in the cell. Spontaneous translation errors are very rare due to stringent selection of cognate aminoacyl transfer RNAs (tRNAs) and the tight control of the mRNA reading frame by the ribosome. Recoding events, such as stop codon readthrough, frameshifting, and translational bypassing, reprogram the
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Quantitative Single-Molecule Localization Microscopy Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Siewert Hugelier, P.L. Colosi, Melike Lakadamyali
Super-resolution fluorescence microscopy allows the investigation of cellular structures at nanoscale resolution using light. Current developments in super-resolution microscopy have focused on reliable quantification of the underlying biological data. In this review, we first describe the basic principles of super-resolution microscopy techniques such as stimulated emission depletion (STED) microscopy
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Bringing Structure to Cell Biology with Cryo-Electron Tomography Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Lindsey N. Young, Elizabeth Villa
Recent advances in cryo-electron microscopy have marked only the beginning of the potential of this technique. To bring structure into cell biology, the modality of cryo-electron tomography has fast developed into a bona fide in situ structural biology technique where structures are determined in their native environment, the cell. Nearly every step of the cryo-focused ion beam-assisted electron tomography
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Emerging Time-Resolved X-Ray Diffraction Approaches for Protein Dynamics Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Doeke R. Hekstra
Proteins guide the flows of information, energy, and matter that make life possible by accelerating transport and chemical reactions, by allosterically modulating these reactions, and by forming dynamic supramolecular assemblies. In these roles, conformational change underlies functional transitions. Time-resolved X-ray diffraction methods characterize these transitions either by directly triggering
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Protein Diffusion Along Protein and DNA Lattices: Role of Electrostatics and Disordered Regions Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-05-09 Lavi S. Bigman, Yaakov Levy
Diffusion is a pervasive process present in a broad spectrum of cellular reactions. Its mathematical description has existed for nearly two centuries and permits the construction of simple rules for evaluating the characteristic timescales of diffusive processes and some of their determinants. Although the term diffusion originally referred to random motions in three-dimensional (3D) media, several
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Theoretical and Practical Aspects of Multienzyme Organization and Encapsulation Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-02-28 Charlotte H. Abrahamson, Brett J. Palmero, Nolan W. Kennedy, Danielle Tullman-Ercek
The advent of biotechnology has enabled metabolic engineers to assemble heterologous pathways in cells to produce a variety of products of industrial relevance, often in a sustainable way. However, many pathways face challenges of low product yield. These pathways often suffer from issues that are difficult to optimize, such as low pathway flux and off-target pathway consumption of intermediates. These
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Fifty Years of Biophysics at the Membrane Frontier Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-02-15 Stephen H. White
The author first describes his childhood in the South and the ways in which it fostered the values he has espoused throughout his life, his development of a keen fascination with science, and the influences that supported his progress toward higher education. His experiences in ROTC as a student, followed by two years in the US Army during the Vietnam War, honed his leadership skills. The bulk of the
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Graphene and Two-Dimensional Materials for Biomolecule Sensing Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-02-15 Deependra Kumar Ban, Prabhakar R. Bandaru
An ideal biosensor material at room temperature, with an extremely large surface area per unit mass combined with the possibility of harnessing quantum mechanical attributes, would be comprised of graphene and other two-dimensional (2D) materials. The sensing of a variety of sizes and types of biomolecules involves modulation of the electrical charge density of (current through) the 2D material and
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Hybrid Quantum Mechanical/Molecular Mechanical Methods For Studying Energy Transduction in Biomolecular Machines Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-02-15 T. Kubař, M. Elstner, Q. Cui
Hybrid quantum mechanical/molecular mechanical (QM/MM) methods have become indispensable tools for the study of biomolecules. In this article, we briefly review the basic methodological details of QM/MM approaches and discuss their applications to various energy transduction problems in biomolecular machines, such as long-range proton transports, fast electron transfers, and mechanochemical coupling
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Interaction Dynamics of Intrinsically Disordered Proteins from Single-Molecule Spectroscopy Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-02-08 Aritra Chowdhury, Daniel Nettels, Benjamin Schuler
Many proteins contain large structurally disordered regions or are entirely disordered under physiological conditions. The functions of these intrinsically disordered proteins (IDPs) often involve interactions with other biomolecules. An important emerging effort has thus been to identify the molecular mechanisms of IDP interactions and how they differ from the textbook notions of biomolecular binding
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On the Rational Design of Cooperative Receptors Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-02-04 Gabriel Ortega, Alejandro Chamorro-Garcia, Francesco Ricci, Kevin W. Plaxco
Cooperativity (homotropic allostery) is the primary mechanism by which evolution steepens the binding curves of biomolecular receptors to produce more responsive input–output behavior in biomolecular systems. Motivated by the ubiquity with which nature employs this effect, over the past 15 years we, together with other groups, have engineered this mechanism into several otherwise noncooperative receptors
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Structure and Mechanism of Human ABC Transporters Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-02-04 Amer Alam, Kaspar P. Locher
ABC transporters are essential for cellular physiology. Humans have 48 ABC genes organized into seven distinct families. Of these genes, 44 (in five distinct families) encode for membrane transporters, of which several are involved in drug resistance and disease pathways resulting from transporter dysfunction. Over the last decade, advances in structural biology have vastly expanded our mechanistic
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Simulation of Complex Biomolecular Systems: The Ribosome Challenge Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-31 Lars V. Bock, Sara Gabrielli, Michal H. Kolář, Helmut Grubmüller
Large biomolecular systems are at the heart of many essential cellular processes. The dynamics and energetics of an increasing number of these systems are being studied by computer simulations. Pushing the limits of length- and timescales that can be accessed by current hard- and software has expanded the ability to describe biomolecules at different levels of detail. We focus in this review on the
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Cryo-Electron Tomography: The Resolution Revolution and a Surge of In Situ Virological Discoveries Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-31 Ye Hong, Yutong Song, Zheyuan Zhang, Sai Li
The recent proliferation of cryo-electron tomography (cryo-ET) techniques has led to the cryo-ET resolution revolution. Meanwhile, significant efforts have been made to improve the identification of targets in the cellular context and the throughput of cryo-focused ion beam (FIB) milling. Together, these developments led to a surge of in situ discoveries on how enveloped viruses are assembled and how
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HX and Me: Understanding Allostery, Folding, and Protein Machines Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-11 S. Walter Englander
My accidental encounter with protein hydrogen exchange (HX) at its very beginning and its continued development through my scientific career have led us to a series of advances in HX measurement, interpretation, and cutting edge biophysical applications. After some thoughts about how life brought me there, I take the opportunity to reflect on our early studies of allosteric structure and energy change
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Coding From Binding? Molecular Interactions at the Heart of Translation Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-10 Bojan Zagrovic, Marlene Adlhart, Thomas H. Kapral
The mechanism and the evolution of DNA replication and transcription, the key elements of the central dogma of biology, are fundamentally well explained by the physicochemical complementarity between strands of nucleic acids. However, the determinants that have shaped the third part of the dogma—the process of biological translation and the universal genetic code—remain unclear. We review and seek
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Critical Assessment of Methods for Predicting the 3D Structure of Proteins and Protein Complexes Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-10 Shoshana J. Wodak, Sandor Vajda, Marc F. Lensink, Dima Kozakov, Paul A. Bates
Advances in a scientific discipline are often measured by small, incremental steps. In this review, we report on two intertwined disciplines in the protein structure prediction field, modeling of single chains and modeling of complexes, that have over decades emulated this pattern, as monitored by the community-wide blind prediction experiments CASP and CAPRI. However, over the past few years, dramatic
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Assembly and Architecture of NLR Resistosomes and Inflammasomes Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-10 Zehan Hu, Jijie Chai
Nucleotide-binding and leucine-rich repeat (NLR) proteins are critical intracellular immune receptors in both animals and plants. Perception of pathogen-derived or stress-associated signals induces NLR oligomerization to form multiprotein complexes called inflammasomes in animals or resistosomes in plants to mediate host immune response. Significant progress has been made during the past few years
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Ball-and-Chain Inactivation in Potassium Channels Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-10 Nattakan Sukomon, Chen Fan, Crina M. Nimigean
Carefully orchestrated opening and closing of ion channels control the diffusion of ions across cell membranes, generating the electrical signals required for fast transmission of information throughout the nervous system. Inactivation is a parsimonious means for channels to restrict ion conduction without the need to remove the activating stimulus. Voltage-gated channel inactivation plays crucial
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Free Energy Methods for the Description of Molecular Processes Annu. Rev. Biophys. (IF 12.4) Pub Date : 2023-01-10 Christophe Chipot
Efforts to combine theory and experiment to advance our knowledge of molecular processes relevant to biophysics have been considerably enhanced by the contribution of statistical-mechanics simulations. Key to the understanding of such molecular processes is the underlying free-energy change. Being able to accurately predict this change from first principles represents an appealing prospect. Over the
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Chiral Induced Spin Selectivity and Its Implications for Biological Functions Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-05-09 Ron Naaman, Yossi Paltiel, David H. Waldeck
Chirality in life has been preserved throughout evolution. It has been assumed that the main function of chirality is its contribution to structural properties. In the past two decades, however, it has been established that chiral molecules possess unique electronic properties. Electrons that pass through chiral molecules, or even charge displacements within a chiral molecule, do so in a manner that
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Mapping Enzyme Landscapes by Time-Resolved Crystallography with Synchrotron and X-Ray Free Electron Laser Light Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-05-09 Mark A. Wilson
Directly observing enzyme catalysis in real time at the molecular level has been a long-standing goal of structural enzymology. Time-resolved serial crystallography methods at synchrotron and X-ray free electron laser (XFEL) sources have enabled researchers to follow enzyme catalysis and other nonequilibrium events at ambient conditions with unprecedented time resolution. X-ray crystallography provides
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Variable-Temperature Native Mass Spectrometry for Studies of Protein Folding, Stabilities, Assembly, and Molecular Interactions Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-05-09 Arthur Laganowsky, David E. Clemmer, David H. Russell
The structures and conformational dynamics of proteins, protein complexes, and their noncovalent interactions with other molecules are controlled specifically by the Gibbs free energy (entropy and enthalpy) of the system. For some organisms, temperature is highly regulated, but the majority of biophysical studies are carried out at room, nonphysiological temperature. In this review, we describe variable-temperature
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Phospholipid Scrambling by G Protein–Coupled Receptors Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-05-09 George Khelashvili, Anant K. Menon
Rapid flip-flop of phospholipids across the two leaflets of biological membranes is crucial for many aspects of cellular life. The transport proteins that facilitate this process are classified as pump-like flippases and floppases and channel-like scramblases. Unexpectedly, Class A G protein–coupled receptors (GPCRs), a large class of signaling proteins exemplified by the visual receptor rhodopsin
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Enzymology and Dynamics by Cryogenic Electron Microscopy Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-05-09 Ming-Daw Tsai, Wen-Jin Wu, Meng-Chiao Ho
Cryogenic electron microscopy (cryo-EM) has revolutionized the field of structural biology, particularly in solving the structures of large protein complexes or cellular machineries that play important biological functions. This review focuses on the contribution and future potential of cryo-EM in related emerging applications—enzymatic mechanisms and dynamic processes. Work on these subjects can benefit
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A Life of Biophysics Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-05-09 Bertil Hille
Biophysics is a way of approaching biological problems through numbers, physical laws, models, and quantitative logic. In a long scientific career, I have seen the formation and fruition of the ion channel concept through biophysical study. Marvelous discoveries were made as our instruments evolved from vacuum tubes to transistors; computers evolved from the size of an entire building to a few chips
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The Effects of Temperature on Cellular Physiology Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-05-09 Benjamin D. Knapp, Kerwyn Casey Huang
Temperature impacts biological systems across all length and timescales. Cells and the enzymes that comprise them respond to temperature fluctuations on short timescales, and temperature can affect protein folding, the molecular composition of cells, and volume expansion. Entire ecosystems exhibit temperature-dependent behaviors, and global warming threatens to disrupt thermal homeostasis in microbes
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Macromolecular Crowding Is More than Hard-Core Repulsions Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-03-03 Shannon L. Speer, Claire J. Stewart, Liel Sapir, Daniel Harries, Gary J. Pielak
Cells are crowded, but proteins are almost always studied in dilute aqueous buffer. We review the experimental evidence that crowding affects the equilibrium thermodynamics of protein stability and protein association and discuss the theories employed to explain these observations. In doing so, we highlight differences between synthetic polymers and biologically relevant crowders. Theories based on
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Molecular Shape Solution for Mesoscopic Remodeling of Cellular Membranes Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-03-03 Pavel V. Bashkirov, Peter I. Kuzmin, Javier Vera Lillo, Vadim A. Frolov
Cellular membranes self-assemble from and interact with various molecular species. Each molecule locally shapes the lipid bilayer, the soft elastic core of cellular membranes. The dynamic architecture of intracellular membrane systems is based on elastic transformations and lateral redistribution of these elementary shapes, driven by chemical and curvature stress gradients. The minimization of the
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ATP-Independent Chaperones Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-02-15 Rishav Mitra, Kevin Wu, Changhan Lee, James C.A. Bardwell
The folding of proteins into their native structure is crucial for the functioning of all biological processes. Molecular chaperones are guardians of the proteome that assist in protein folding and prevent the accumulation of aberrant protein conformations that can lead to proteotoxicity. ATP-independent chaperones do not require ATP to regulate their functional cycle. Although these chaperones have
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Molecular Mechanisms Underlying Neurotransmitter Release Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-02-15 Josep Rizo
Major recent advances and previous data have led to a plausible model of how key proteins mediate neurotransmitter release. In this model, the soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) proteins syntaxin-1, SNAP-25, and synaptobrevin form tight complexes that bring the membranes together and are crucial for membrane fusion. NSF and SNAPs disassemble SNARE
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Insights into the Thermodynamics and Kinetics of Amino-Acid Radicals in Proteins Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-02-08 Cecilia Tommos
Some oxidoreductase enzymes use redox-active tyrosine, tryptophan, cysteine, and/or glycine residues as one-electron, high-potential redox (radical) cofactors. Amino-acid radical cofactors typically perform one of four tasks—they work in concert with a metallocofactor to carry out a multielectron redox process, serve as storage sites for oxidizing equivalents, activate the substrate molecules, or move
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Orientation of Cell Polarity by Chemical Gradients Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-02-07 Debraj Ghose, Timothy Elston, Daniel Lew
Accurate decoding of spatial chemical landscapes is critical for many cell functions. Eukaryotic cells decode local chemical gradients to orient growth or movement in productive directions. Recent work on yeast model systems, whose gradient sensing pathways display much less complexity than those in animal cells, has suggested new paradigms for how these very small cells successfully exploit information
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Waves in Embryonic Development Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-02-04 Stefano Di Talia, Massimo Vergassola
Embryonic development hinges on effective coordination of molecular events across space and time. Waves have recently emerged as constituting an ubiquitous mechanism that ensures rapid spreading of regulatory signals across embryos, as well as reliable control of their patterning, namely, for the emergence of body plan structures. In this article, we review a selection of recent quantitative work on
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Rules of Physical Mathematics Govern Intrinsically Disordered Proteins Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-02-04 Kingshuk Ghosh, Jonathan Huihui, Michael Phillips, Austin Haider
In stark contrast to foldable proteins with a unique folded state, intrinsically disordered proteins and regions (IDPs) persist in perpetually disordered ensembles. Yet an IDP ensemble has conformational features—even when averaged—that are specific to its sequence. In fact, subtle changes in an IDP sequence can modulate its conformational features and its function. Recent advances in theoretical physics
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Super-Resolution Microscopy for Structural Cell Biology Annu. Rev. Biophys. (IF 12.4) Pub Date : 2022-02-04 Sheng Liu, Philipp Hoess, Jonas Ries
Super-resolution microscopy techniques, and specifically single-molecule localization microscopy (SMLM), are approaching nanometer resolution inside cells and thus have great potential to complement structural biology techniques such as electron microscopy for structural cell biology. In this review, we introduce the different flavors of super-resolution microscopy, with a special emphasis on SMLM