Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase

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Highlights? The crystal structure of the heterotetrameric CRL3-SPOP ubiquitin ligase is reported ? Substrate adaptor proteins are recruited to CRL complexes through a signature motif ? Tandem BTB and BACK domains potentiate assembly and activity of the CRL3-SPOP ligase ? The SPOPL negative regulator creates a molecular rheostat to fine-tune CRL3 activity     

Structure of AAV-DJ, a Retargeted Gene Therapy Vector: Cryo-Electron Microscopy at 4.5 Å Resolution

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Highlights? The 4.5 Å cryo-EM structure of AAV-DJ fully resolves the polypeptide backbone ? Liver tropism selected for in AAV-DJ has not changed the heparin binding site ? Changed conformation in an antigenic loop blocks binding of a neutralizing mAb ? Changed in vivo tropism may result from changed immune interactions     

ATP alters the diffusion mechanics of MutS on mismatched DNA

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Highlights? The development and use of smFlow-FRET and smPolarization-TIRF microscopy ? Lesion-searching MutS rotationally diffuses in continuous contact with the DNA ? ATP-bound MutS spins freely and in discontinuous contact with the DNA backbone ? Direct visualization of multiple ATP-bound MutS clamps that diffuse along the DNA     

Homeodomain-interacting protein kinase regulates yorkie activity to promote tissue growth

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Highlights? Hipk induces tissues overgrowth and leads to activation of Yki target genes ? Hipk is required for activity of hyperactive Yki ? Hipk kinase function is essential to promote Yki target genes     

A position-specific distance-dependent statistical potential for protein structure and functional study

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Highlights? Protein and position-specific statistical potentials are more powerful ? Evolutionary information greatly boost performance of statistical potentials ? Observed probability is critical to energy potentials, in addition to reference state ? Observed probability can be estimated better using context-specific information     

A protein export pathway involving Escherichia coli porins

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Highlights? The porin OmpF is a required element for the secretion of YebF ? YebF interacts with OmpF and OmpC channels at their periplasmic face ? YebF exhibits a dynamic surface that is involved in the secretion process ? Proposed model of YebF secretion mediated by OmpF     

Stonin 2 is a major adaptor protein for clathrin-mediated synaptic vesicle retrieval

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Highlights? Targeted RNAi screen of adaptors for vesicle retrieval at hippocampal synapses ? Stonin 2 is a major adaptor for clathrin-mediated retrieval of synaptic vesicles ? Rapid, induced rerouting of stonin 2 demonstrates the role of this adaptor     

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     

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     

Mutational tipping points for switching protein folds and functions

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Highlights? Switching between 3α and 4β+α folds can occur in multiple ways ? Single-residue mutations at diverse positions can induce fold switching ? Mutations lead to a near-complete shift in equilibrium between the two folds ? New function can be gained before the relevant fold is significantly populated     

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     

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     

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     

Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation

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Highlights? Cocrystal structure of KRIT1 with ICAP1 shows a bidentate interaction interface ? Cocrystal structure of ICAP1 with integrin β1 shows a PTB-peptide interaction ? KRIT1 antagonizes ICAP1-modulated integrin activation by the bidentate interaction ? KRIT1 contains a previously undescribed N-terminal Nudix domain     

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     

Screening and in situ synthesis using crystals of a NAD kinase lead to a potent antistaphylococcal compound

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Highlights? Precise interaction mapping using substrate analogs and X-ray crystallography ? Amidation of 5′-amino-5′-deoxy-adenosine is promoted by crystallized LmNADK1 ? Structures guide fragment bridging to design a new antistaphylococcal compound     

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     

Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCι in complex with a substrate peptide from Par-3

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Highlights? The 3D structure of PKCι in complex with a peptide from Par-3 is determined ? PKCι does not need phosphorylation of Thr402 in its activation loop for its activity ? aPKCs do not need a priming kinase for their activations ? The PKCι/Par-3 structure reveals a unique substrate recognition patterns for aPKCs     

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     

Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases

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Highlights? Crystal structure of CCM3-MST4 heterodimeric complex ? Structural mechanism driving CCM3-GCKIII heterodimerization ? Conformational changes required for CCM3-GCKIII heterodimerization ? Synergistic effects of CCM3-MST4 complex on cell proliferation and migration