Identification of the Outer-Inner Dynein Linker as a Hub Controller for Axonemal Dynein Activities

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Highlights? Outer dynein intermediate chain 2 (IC2) forms the outer-inner dynein (OID) linker ? A mutation to IC2 nonspecifically activates the outer dynein activity ? The mutation to IC2 alters the inner-dynein-dependent flagellar waveform ? The OID linker regulates flagellar beating by controlling outer and inner dyneins     

ATP-Driven Remodeling of the Linker Domain in the Dynein Motor

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Highlights? Structural changes in axonemal and cytoplasmic dynein motors seen by cryo-EM ? Movement is amplified by a hinge action within dynein's linker domain ? The linker is a stable structure that is actively remodeled by dynein's AAA+ modules ? Dynein's neck subdomain interacts with AAA4 and is an intrinsic site of flexibility     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

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Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

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     

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 Crystal Structure of the Catalytic Domain of the NF-κB Inducing Kinase Reveals a Narrow but Flexible Active Site

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Highlights? Production of soluble NIK kinase domain ? Structures of apo murine and human NIK possess active conformation ? Structure of mNIK bound to inhibitors reveals conformational flexibility ? Inhibitor potency varies against mNIK and hNIK due to substitution in the active site     

Protein Conformation Ensembles Monitored by HDX Reveal a Structural Rationale for Abscisic Acid Signaling Protein Affinities and Activities

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Highlights? Conformations support PYL2 “gate” role in dimerization and phosphatase inhibition ? Structural mechanism of ABA-PYL2 affinity for HAB1 over kinases linked to Trp lock ? HDX suggests kinase activity is associated with a stable “closed” conformation     

Crystallographic and NMR Evidence for Flexibility in Oligosaccharyltransferases and Its Catalytic Significance

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Highlights? OST transfers an oligosaccharide chain to the Asn-X-Ser/Thr sequons in proteins ? A plastic segment found in crystal structures underwent dynamic motions in solution ? An engineered disulfide bond that locked the conformation abolished the OST activity ? Dynamic sequon recognition is implicated in efficient cotranslational N-glycosylation     

Supertertiary Structure of the MAGUK Core from PSD-95

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Highlights? Using NMR and SAXS, we depict the dynamic structure of the MAGUK core PSD-95 ? PDZ3 of the MAGUK core interacts with SH3 via its canonical peptide binding groove ? Binding of PDZ peptides, such as CRIPT, disrupts the interaction between PDZ3 and SH3 ? Rosetta modeling shows that linker residues L411/M412 dock into the PDZ3 binding site     

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     

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     

FANCM and FAAP24 Maintain Genome Stability via Cooperative as Well as Unique Functions

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Highlights? FANCM and FAAP24 exhibit nonepistatic functions in cell survival upon DNA damage ? FAAP24 confers unique lesion specificity in DNA damage cell-cycle checkpoint ? FANCM translocase activity is involved in recombination-independent ICL repair     

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     

A Matrix Protein Silences Transposons and Repeats through Interaction with Retinoblastoma-Associated Proteins

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Highlights? The Arabidopsis matrix protein TEK silences transposons and repeat-containing genes ? Binding of TEK on targets affects chromatin conformation and histone modifications ? TEK protein associates with FVE/MSI5-containing histone deacetylation complex ? TEK directs repressive modification as a key structural component in gene silencing     

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     

The Structure of the Tiam1 PDZ Domain/ Phospho-Syndecan1 Complex Reveals a Ligand Conformation that Modulates Protein Dynamics

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Highlights? The Tiam1 PDZ domain preferentially binds a subset of syndecan (SDC) proteins ? The PDZ domain/phospho-SDC1 structure reveals a phosphoryl binding pocket ? Ligand specificity and phosphorylation regulate PDZ/SDC interactions and signaling ? Tiam1 PDZ domain dynamics are ligand-dependent and regulated by phosphorylation     

The SH2 Domain Interaction Landscape

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Highlights? The recognition specificity of 70 SH2 domains is probed ? Recognition specificity diverges faster than sequence ? PepspotDB is a database of protein interactions mediated by SH2 domains     

Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA

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Highlights? Neil3 is an Fpg/Nei DNA glycosylase of the base excision repair pathway ? Neil3 excises a broad spectrum of base lesions, with a marked preference for ssDNA ? We report a crystal structure of Neil3 DNA glycosylase ? The structure provides valuable insights into Neil3′s unusual substrate specificity     

Chemical attenuation of pilus function and assembly in Gram-negative bacteria

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Highlights? The promise of receptor analogues and biogenesis inhibitors to curb adhesive pili. ? Mannoside-based type 1 pilus inhibitors are effective against UPEC in a murine model of UTI. ? Pilus adhesins contain specificity and affinity-determining regions. ? Bi-cyclic 2-pyridones inhibit curli and chaperone–usher pilus biogenesis.