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     

Efficient Retrograde Transport of Pseudorabies Virus within Neurons Requires Local Protein Synthesis in Axons

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Highlights? Pseudorabies virus (PRV) infection stimulates local protein synthesis in axons ? Infection induces the synthesis of LIS1, peripherin, and annexin A2 in axons ? Axonal inhibition of protein synthesis retards retrograde PRV capsid transport ? Prior damage in axons significantly reduces retrograde PRV capsid transport     

Sequence-Specific Transcription Factor NF-Y Displays Histone-like DNA Binding and H2B-like Ubiquitination

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Highlights? 3D structure of NF-Y/CCAAT shows close relationships to core histones H2A/H2B ? NF-YA displays a sequence-specific DNA minor groove-binding module ? Histone H2B and NF-YB share a functional posttranslational modification ? NF-Y binding and monoubiquitination are early events in gene activation     

An Autoinhibited State in the Structure of Thermotoga maritima NusG

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Highlights? Thermotoga maritima NusG shows a dynamic intramolecular NTD-CTD interaction ? The NTD-CTD interaction hides the binding surfaces for RNA polymerase, S10, and Rho ? Domain interaction contributes to thermostability ? Thermotoga maritima NusG does not complement a NusG-deficient E. coli strain     

Dynamin 2 Potentiates Invasive Migration of Pancreatic Tumor Cells through Stabilization of the Rac1 GEF Vav1

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Highlights? Dyn2 promotes lamellipodia formation and pancreatic tumor cell migration ? Direct binding between Dyn2 and Vav1 promotes Rac1 activation and migration ? Dyn2 binding protects Vav1 from degradation by the lysosome ? Vav1 is targeted for degradation through an interaction with Hsc70     

Recognizing protein-ligand binding sites by global structural alignment and local geometry refinement

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Highlights? A protein-ligand binding method combining structure and evolutionary insights ? Large-scale test and validation on both benchmark and blind experiments ? Comprehensive and deep analysis on what works and what does not ? Ligand binding prediction with accuracy higher than the state-of-the-art methods     

The Mycobacterium tuberculosis very-long-chain fatty acyl-CoA synthetase: structural basis for housing lipid substrates longer than the enzyme

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Highlights? M. tuberculosis FadD13 is a peripheral membrane protein ? Mutagenesis reveals an arginine-rich patch as the site for membrane interaction ? A hydrophobic tunnel extends from the active site to the positively charged patch ? The architecture lets substrates reside partly in the membrane during catalysis     

Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation

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Highlights? Fbxl10 binds to most CpG islands in ESCs ? Fbxl10 recruits Nspc1 and Ring1B to CpG islands ? The Fbxl10, Nspc1, and Ring1B complex is required for H2A monoubiquitylation ? Fbxl10 is required for proper ESC differentiation     

Recognition of Mono-ADP-Ribosylated ARTD10 Substrates by ARTD8 Macrodomains

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Highlights? ARTD8 macrodomains read ARTD10-dependent mono-ADP-ribosylation ? The structure of ARTD8 macrodomains reveals a conserved fold for ADP-ribose binding ? Distinct macrodomains read mono- and poly-ADP-ribosylation selectively ? ARTD8 macrodomains can be used to visualize mono-ADP-ribosylation in cells     

Activated CaMKII Couples GluN2B and Casein Kinase 2 to Control Synaptic NMDA Receptors

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Highlights? Activated CaMKII recruits CK2 to form a trimolecular complex (GluN2B/CaMKII/CK2) ? GluN2B/CaMKII binding controls CK2 phosphorylation of the GluN2B PDZ ligand (S1480) ? Disruption of GluN2B/CaMKII binding increases GluN2B surface expression ? GluN2B/CaMKII binding drives synaptic GluN2B clearance     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

Microautophagy of cytosolic proteins by late endosomes

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Highlights? Late endosomes take up cytosolic proteins through membrane invaginations ? Endosomal microautophagy (eMI) requires multivesicular body formation ? hsc70 mediates selective targeting of cytosolic proteins during eMI ? hsc70 binds to the endosomal membrane through its polybasic cluster     

Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy

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Highlights? We have determined the cryo-EM structures of ORC, ORC-DNA, and ORC-Cdc6-DNA ? We show that ORC is arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to Orc2 ? DNA and Cdc6 binding causes large conformational changes in ORC ? Origin DNA is proposed to bind to the interior surface of the crescent-shaped ORC     

Molecular mechanism for inhibition of g protein-coupled receptor kinase 2 by a selective RNA aptamer

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Highlights? C13 RNA aptamer variants stabilize GRK2 in a unique and remodeled conformation ? The aptamer positions an adenine nucleotide into the ATP-binding pocket of GRK2 ? Basic residues on an exterior surface of GRK2 facilitate aptamer binding ? The terminal stem of the aptamer indirectly contributes to affinity     

DAD2 Is an α/β Hydrolase Likely to Be Involved in the Perception of the Plant Branching Hormone,Strigolactone

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Highlights? DAD2 gene, identified by transposon tagging, encodes an α/β hydrolase fold protein ? DAD2 acts in the shoot; mutants are insensitive to strigolactones ? DAD2 crystal structure shows an internal cavity capable of binding strigolactones ? DAD2 can hydrolyze the strigolactone GR24     

Molecular and structural basis of ESCRT-III recruitment to membranes during archaeal cell division

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Highlights? A conserved protein, CdvA, recruits ESCRT-III to membranes during cell division ? Recruitment is mediated by a peptide-winged helix domain interaction ? We have determined the structure of this complex ? CdvA and a single ESCRT-III protein can drive membrane deformation in vitro     

Genetic Correction of a LRRK2 Mutation in Human iPSCs Links Parkinsonian Neurodegeneration to ERK-Dependent Changes in Gene Expression

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Highlights? hiPSC-derived neurons with LRRK2 G2019S exhibit Parkinsonian neurodegeneration ? Genetic correction of the LRRK2 mutation rescued neurodegenerative phenotypes ? Comparative analysis links LRRK2 G2019S, gene dysregulation, and ERK activation ? ERK-dependent gene dysregulation by LRRK2 G2019S contributes to neurodegeneration     

Structures of adnectin/protein complexes reveal an expanded binding footprint

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Highlights? Adnectins interact with targets using multiple binding modes ? Residues outside of the diversified loops can interact with ligand ? Some fixed scaffold residues contribute to the binding energy ? Adnectins can interact with epitopes that may be inaccessible to antibodies