Structure of NPP1, an Ectonucleotide Pyrophosphatase/Phosphodiesterase Involved in Tissue Calcification

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Highlights? We determine the crystal structure of mouse NPP1 ? We elucidate the mechanism of NPP1 dimer formation and secretion ? The structure explains the dramatic functional differences between NPP1 and NPP2 ? The structure allows defining the impact of pathogenic mutations in human NPP1     

Anions Mediate Ligand Binding in Adineta vaga Glutamate Receptor Ion Channels

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Highlights? The AvGluR1 LBD is a hybrid structure with iGluR prokaryotic and eukaryotic features ? AvGluR1 binds hydrophobic amino acids as well as glutamate ? Chloride ions acts as surrogate ligand atoms in the Ala, Ser, and Met complexes ? The AvGluR1 LBD assembles as a dimer but with very low affinity     

A Role for Intersubunit Interactions in Maintaining SAGA Deubiquitinating Module Structure and Activity

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Highlights? Structures of the SAGA deubiquitinating module lacking the Sgf11 zinc finger domain ? The DUB module lacking the Sgf11 zinc finger forms a domain swapped complex dimer ? The conformational changes accompanying domain-swapping disrupt the active site ? Activating mutations in Ubp8 promote the compact form of the DUB module     

The structure of dimeric apolipoprotein A-IV and its mechanism of self-association

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Highlights? Structure of dimeric apoA-IV solved to 2.4 Å by X-ray crystallography ? Structure confirmed through biochemical and mutational analysis ? Understanding of apoA-IV dimerization allowed us to create a monomeric mutant ? Structural features in the dimer offer clues to the genesis of apoA-IV lipoproteins     

Asymmetric mode of Ca²⁺-S100A4 interaction with nonmuscle myosin IIA generates nanomolar affinity required for filament remodeling

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Highlights? S100A4 dimer binds single-myosin IIA molecule in an asymmetrical mode ? Synergy between Ca-dependent sites in S100A4 leads to high-affinity interaction ? Electron microscopy shows that two S100A4 dimers bind to the myosin coiled coil ? S100A4 has direct effect on formation of stress fibers and cell migration     

Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function

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Highlights? Antiparallel dimeric conformation critical for FOXP3 suppressive function ? IPEX mutations disrupted defined intersubunit bonding of the FOXP3 dimer ? Lysine acetylation modulate the intersubunit bonding of the FOXP3 dimer ? Mechanistic model explaining FOXP3 biology and pathology.     

Structure and Ubiquitination-Dependent Activation of TANK-Binding Kinase 1

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Highlights? TBK1 forms a dimer structurally distinct from IKKβ ? Structure of TBK1 with inhibitors reveals basis for specific inhibition ? TBK1 is K63 polyubiquitinated on Lys30 in the kinase domain and Lys401 in the scaffold/dimerization domain ? K63-linked ubiquitination of dimerized TBK1 is required for kinase activation and signaling     

Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I

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Highlights? Crystallographic structure of RIG-I with 5′ triphosphorylated RNA duplex and ADP ? Solution biophysical analysis of ATP-dependent RIG-I conformational change ? The structural basis for ATP-stimulated RIG-I activation     

The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b

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Highlights? The CDK9 C-terminal tail is important for the catalytic mechanism ? CDK9 phosphorylates the CTD in a nonprocessive manner ? The CDK9 tail folds over the ATP binding site during the catalytic cycle     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

The WW Domain Protein Kibra Acts Upstream of Hippo in Drosophila

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Highlights? The WW domain protein Kibra is a Hippo signalling component ? Kibra restricts organ size via Yorkie and acts upstream of Hippo and Merlin ? Kibra synergizes with Expanded and binds to Merlin     

Structure of the Essential Diversity-Generating Retroelement Protein bAvd and Its Functionally Important Interaction with Reverse Transcriptase

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Highlights? bAvd forms a highly positively charged pentameric barrel ? bAvd binds both DNA and RNA, but without sequence preference ? The coding sequence for bAvd serves dual purposes ? The interaction of bAvd with bRT is likely to be important for retrohoming     

A Network Model of the Molecular Organization of Chromatin in Drosophila

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Highlights? DamID identifies 42 previously unknown chromatin proteins ? Binding maps of new and known chromatin components yield a chromatin network model ? The network model predicts functions of most of the 42 new chromatin proteins ? The chromatin protein network is functionally compartmentalized     

Structure and Dynamics of the Second CARD of Human RIG-I Provide Mechanistic Insights into Regulation of RIG-I Activation

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Highlights? The structure of a CARD of human RIG-I ? The mechanism and structural role of phosphorylation are revealed ? In trans interaction with the Helicase and regulatory domains is shown ? Lys172 lies in proximity to the CARD2:helicase-CTD interface     

Evidence for Geomagnetic Imprinting as a Homing Mechanism in Pacific Salmon

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Highlights? Sockeye salmon use geomagnetic imprinting as a homing mechanism ? The homing route of salmon is predicted by magnetic field drift (secular variation)     

Plasma Membrane Tethering of the Cortical ER Necessitates Its Finely Reticulated Architecture

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Highlights? The VAP proteins sustain the ER-plasma membrane attachment in fission yeast ? Footprint of the ER on the cortex is functionally insulated from the cytosol ? Division-site placement requires a patchwork of cortical sites accessible to cytosol     

The Cotranslational Function of Ribosome-Associated Hsp70 in Eukaryotic Protein Homeostasis

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Highlights? Yeast Hsp70 SSB binds cotranslationally to a defined set of nascent polypeptides ? SSB shows specificity for substrates highly challenged in cotranslational folding ? The heterodimeric cochaperone RAC modulates cotranslational SSB specificity ? Loss of SSB function leads to widespread misfolding and aggregation     

The Molecular Basis for Substrate Specificity of the Nuclear NIPP1:PP1 Holoenzyme

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Highlights? The first structure of a nuclear PP1 holoenzyme, NIPP1:PP1 ? The NIPP1 helix defines a unique interaction site on PP1 ? Identification of a common PP1-binding pocket, the ΦΦ motif-binding pocket ? Explains the mechanism of nuclear substrate selection by PP1     

Functional identification of optimized RNAi triggers using a massively parallel sensor assay

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Highlights? The Sensor assay reliably identifies potent single-copy shRNAs ? Potent shRNAs are rare and generally not predicted by existing algorithms ? Analyses of ～20,000 shRNAs reveal insights into shRNA biogenesis and function ? Sensor-based rules provide a criteria framework for rational shRNA design