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 structure determination a challenging task. Thus, an integrative structural and molecular biology approach is required, tackling three key challenges: (1) identification of cognate RNA sequences; (2) collection of structural data by conducting X-ray crystallography, NMR, electron microscopy, small-angle scattering (SAS), and other experiments; and (3) the creation of structural models that integrates all experimental restraints. Given the breadth of expertise required, this review presents an overview of available methods and successful examples with the goal to provide readers with a selection of promising options for structure determination of RNPs.

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, fluctuation profile matching, and the Wiener-Khintchine theorem are used to define the “time periods,” t, for anharmonic principal components (PCs), which are validated by nuclear magnetic resonance (NMR) order parameters. The PCs with their respective “time periods” are mapped to the eigenvalues (λENM) of the corresponding ENM modes. Thus, the power laws t(ns) = 56.1λENM−1.6 and σ2(Å2) = 32.7λENM−3.0 can be established allowing the characterization of the timescales of NMR-resolved conformers, crystallographic anisotropic displacement parameters, and important ribosomal motions, as well as motional sizes of the latter.

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. The primary goal of the Workshop was to build consensus for addressing the challenges involved in creating common data standards, building methods for federated data exchange, and developing mechanisms for validating integrative structures. The summary of the Workshop and the recommendations that emerged are presented here.

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 factors. However, only a limited number of cytoplasmic EGFR modulators are known and a comprehensive understanding of their mode of action is lacking. Here, we report ARNO, a member of the cytohesin family, as another JM-binding protein and structurally characterize the ARNO-EGFR interaction interface. We reveal that its binding mode displays common features and distinct differences with JM's interaction with calmodulin and anionic phospholipids. Furthermore, we show that each interaction can be modulated by additional factors, generating a distinctly regulated network of possible EGFR modulators acting on the intracellular domain of the receptor.

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.

Transmembrane integrin bridges the extracellular and intracellular environments and is activated by focal adhesion proteins, talin and kindlin. Activated integrin engages ligands from the extracellular matrix and controls intracellular responses. In this issue of Structure, Zhu et al. (2019) describe an initial step involving recruitment of paxillin by ubiquitin-like kindlin-2 domain.

In this issue of Structure, Zhou et al. (2019) determine the crystal and solution structures of iASPP bound to PP1. The proteins interact through a discontinuous interface defined by four contact points. Association/dissociation of individual contacts enables the transition between multiple conformations and provides mechanistic insight into how ASPPs regulate phosphorylation of p53.

The small program Illustrate generates non-photorealistic images of biological molecules for use in dissemination, outreach, and education. The method has been used as part of the “Molecule of the Month,” an ongoing educational column at the RCSB Protein Data Bank (http://rcsb.org). Insights from 20 years of application of the program are presented, and the program has been released both as open-source Fortran at GitHub and through an interactive web-based interface.