Structures of dNTP Intermediate States during DNA Polymerase Active Site Assembly

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Highlights? Initial nucleotide binding occurs in the open polymerase complex ? Correct and incorrect nucleotides undergo metal-dependent conformational changes ? Watson-Crick base pairing is sampled upon nucleotide binding ? The stabilization of the correct, but not incorrect, nucleotide deters misinsertion     

Leukemia Fusion Target AF9 Is an Intrinsically Disordered Transcriptional Regulator that Recruits Multiple Partners via Coupled Folding and Binding

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Highlights? The AF9 AHD is intrinsically disordered ? The AHD recruits AF4, BCoR, Dot1L, and hPC3 by coupled folding and binding ? AF9 binding partners compete for binding to a common site ? Dynamics of the AF4-AF9 complex may facilitate exchange between partners     

Finding Protein Targets for Small Biologically Relevant Ligands across Fold Space Using Inverse Ligand Binding Predictions

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Highlights? Inverse ligand binding prediction is implemented with modern binding site predictors ? Use of just one protein-ligand complex allows accurate identification of other protein targets ? Inverse prediction is effective in finding structurally distant protein targets ? Consensus approach provides improvements     

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     

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     

Solution Conformations of Prototype Foamy Virus Integrase and Its Stable Synaptic Complex with U5 Viral DNA

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Highlights? Missing domains in PFV intasome revealed by SAXS/SANS ? PFV IN undergoes dramatic changes in conformation and oligomerization upon binding DNA ? Strand transfer inhibitors do not alter quaternary structure of PFV intasome     

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     

Design of a Phosphorylatable PDZ Domain with Peptide-Specific Affinity Changes

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Highlights? Successful design of phosphorylation sites into a globular protein ? Redesigned PDZ domain phosphorylation is associated with local destabilization ? Phosphorylation switches peptide binding function ? Phosphorylation switches peptide recognition specificity     

Allosteric Mechanism Controls Traffic in the Chaperone/Usher Pathway

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Highlights? Allosteric mechanism controls traffic in the chaperone/usher pathway ? Usher-binding site in free chaperone is conformationally locked ? Subunit binding opens the lock in the chaperone, allowing usher targeting     

Structural and functional analysis of HtrA1 and its subdomains

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Highlights? IGFBP-like domain structure suggests that it is incompetent for IGF binding ? Kazal-like domain structure shows distorted “P1” loop incompetent for inhibition ? Protease domain shows catalytic readiness in apo form ? SAXS envelope for full-length HtrA1     

Functional Insights from the Crystal Structure of the N-Terminal Domain of the Prototypical Toll Receptor

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Highlights? The N-terminal cap of Toll adopts a new fold ? It resembles a duplicated beta hairpin structure with three disulphide bonds ? Toll LRRNT cap is not critical for Spätzle binding ? The first 13 LRRs are sufficient for Spätzle binding     

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     

Structure of an Asymmetric Ternary Protein Complex Provides Insight for Membrane Interaction

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Highlights? S100A10, annexin A2, and AHNAK are involved in membrane repair ? The AHNAK binding region forms a coiled structure ? Both S100A10 and annexin A2 make contacts to AHNAK and are necessary for binding ? The asymmetric architecture provides a model for AHNAK translocation to the membrane     

The Crystal Structures of the Eukaryotic Chaperonin CCT Reveal Its Functional Partitioning

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Highlights? CCT subunit types can be identified in crystallographic data, even at low resolutions ? Actin and tubulin both bind around CCT6 ? ATP hydrolysis and substrate binding are partitioned in the CCT particle     

Structure of the Pentameric Ligand-Gated Ion Channel GLIC Bound with Anesthetic Ketamine

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Highlights? The structure of ketamine-bound GLIC reveals an anesthetic binding site ? The study provides compelling evidence for allosteric inhibition by anesthetics ? Ketamine inhibition on GLIC is similar to competitive antagonist action on nAChRs ? Ketamine directly acts on pLGICs in addition to NMDA receptors     

Distinct States of Methionyl-tRNA Synthetase Indicate Inhibitor Binding by Conformational Selection

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Highlights? Complexes of MetRS from T. brucei with its substrate, intermediate, and inhibitors ? In crystals, substrate-bound MetRS undergoes extensive changes with inhibitor binding ? The inhibitor-bound conformation is surprisingly similar to the ligand-free state ? This indicates inhibitor binding occurs via conformational selection not by induced fit     

Cotranslational Response to Proteotoxic Stress by Elongation Pausing of Ribosomes

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Highlights? Proteotoxic stress reduces global protein synthesis by influencing elongation ? Proteotoxic stress induces ribosome pausing on mRNAs in the first 50 codons ? Molecular chaperones facilitate translation elongation by binding to nascent chains ? Ribosomes fine tune elongation rate in response to proteotoxic stress     

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