In this issue of Structure, Coulombe and coworkers (Lee et al., 2020) present the crystal structure of the keratin 5/14 2B heterodimeric complex containing the keratin 14 substitution C367A. The authors identify a 2B-2B contact interface important to the elongation of mature keratin 5/14 filaments.

In this issue of Structure, Cai et al. (2020) describe crystal structures of the postsynaptic protein Shank3, a homolog of cortactin binding protein 1 (CBP1), in complex with small G proteins Rap1 and H-Ras. Functional studies suggest that binding of Ras and Rap to Shank3 is modulated by synaptic plasticity.

Ma et al. (2020) and Liang et al. (2020) describe the cryo-EM structures of three class B G protein-coupled receptors (GPCRs) in complex with native peptides and Gs. Their work establishes the structural basis of peptide specificity and a conserved mechanism of receptor activation and G protein coupling for class B GPCRs.

Members of the family Reoviridae package several copies of the viral polymerase complex into their capsid to carry out replication and transcription within viral particles. Classical single-particle reconstruction encounters difficulties resolving structures such as the intraparticle polymerase complex because refinement can converge to an incorrect map and because the map could depict a nonrepresentative

In this issue of Structure, Absmeier et al. (2020) describe the molecular mechanisms employed by an RNA helicase to prevent premature ATP hydrolysis upon nucleotide binding.

Rab8a is associated with the dynamic regulation of membrane protrusions in polarized cells. Rab8a is one of several Rab GTPases that are substrates of leucine-rich repeat kinase 2 (LRRK2), a serine/threonine kinase that is linked to Parkinson's disease. Rab8a is phosphorylated at T72 (pT72) in its switch 2 helix and recruits the phospho-specific effector RILPL2, which subsequently regulates ciliogenesis

Toll-like receptors (TLRs) are pivotal in triggering the innate immune response to pathogen infection. Ligand binding induces receptor dimerization which facilitates the recruitment of other post-receptor signal transducers into a complex signalosome, the Myddosome. Central to this process is Myeloid differentiation primary response 88 (MyD88), which is required by almost all TLRs, and signaling is

K11/K48-branched ubiquitin chains are proteasomal priority signals that elicit the rapid elimination of mitotic regulators and aggregation-prone proteins. Indicative of an intriguing signaling mode, Boughton et al. (2019) unravel an interaction between distal subunits of K11/K48-branched ubiquitin trimers that could provide a combined surface for recognition by the proteasomal receptor RPN1.

Nucleosomes at the centromere contain CENP-A, a histone H3 variant that establishes a specific, yet poorly defined centromeric chromatin architecture. In this issue of Structure, Takizawa et al. (2019) describe an untwisted configuration for an H3-CENP-A-H3 tri-nucleosome that mimics centromeric chromatin. Untwisting may increase centromeric-protein accessibility to CENP-A in compacted chromatin.

Ribonucleoprotein complexes (RNPs) are central to all processes in the cell. One of the prerequisites to understand how RNPs work is to determine their high-resolution structures. With the recent revolution in cryoelectron microscopy this task has become easier for large RNP machines, such as ribosomes, spliceosomes, and polymerases. However, the transient and highly dynamic nature of many RNPs makes

Luteovirids rank among the most destructive viruses of economically important crops. Until now their structures have only been inferred by inadequate homology models due to their phloem-limited infection and inadequate yields. Employing virus-like particles, Byrne et al. (2019) now report near-atomic resolution structures of two family members providing important functional insights.

LARP1 proteins integrate the translation and stability of 5'TOP mRNAs with signaling from the mTOR pathway, but the mechanism is not well understood. In this issue of Structure, Cassidy et al. (2019) propose that the LARP1-DM15 motif modulates access to the 5'TOP mRNA's m7G-ppp-Cytosine cap.

In this issue of Structure, Das et al. (2019) probe the structure and dynamics of dimeric cytohesins (guanine nucleotide exchange factors for ADP-ribosylation factors), in solution and on membranes. Unleashing an arsenal of methods, they demonstrate that a pleckstrin-homology domain-mediated membrane recruitment promotes conformational changes that prime cytohesins for allosteric activation.

Life ticks as fast as how proteins move. Computationally expensive molecular dynamics simulation has been the only theoretical tool to gauge the time and sizes of these motions, though barely to their slowest ends. Here, we convert a computationally cheap elastic network model (ENM) into a molecular timer and sizer to gauge the slowest functional motions of structured biomolecules. Quasi-harmonic analysis

Structures of biomolecular systems are increasingly computed by integrative modeling. In this approach, a structural model is constructed by combining information from multiple sources, including varied experimental methods and prior models. In 2019, a Workshop was held as a Biophysical Society Satellite Meeting to assess progress and discuss further requirements for archiving integrative structures

Epidermal growth factor receptors (EGFRs) are central cellular signaling interfaces whose misregulation is related to several severe diseases. Although ligand binding to the extracellular domain is the most obvious regulatory element, also intracellular factors can act as modulators of EGFR activity. The juxtamembrane (JM) segment seems to be the receptor's key interaction interface of these cytoplasmic

In this issue of Structure, Gucinski et al. (2019) have described structural and enzymatic characterizations of two tRNase ribotoxins. The study significantly advances our understanding on the evolution and the mode of action of a group of ribotoxins that cleave the accepting stem of tRNAs for cell killing.