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     

Mechanism of Origin DNA Recognition and Assembly of an Initiator-Helicase Complex by SV40 Large Tumor Antigen

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Highlights? Cocrystal structure reveals multidomain SV40 large T binding to DNA ? Dimeric LTag bound to origin DNA is intermediate in initiator-helicase assembly ? Interplay among OBD, Zn, and AAA+ domains enables recognition of origin DNA ? DNA shape readout can be mediated through histidine contacts with the minor groove     

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     

β1 Integrin Establishes Endothelial Cell Polarity and Arteriolar Lumen Formation via a Par3-Dependent Mechanism

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Highlights? β1 integrin deletion results in loss of endothelial polarity and vessel patency ? β1 integrin regulates cell-cell adhesion protein distribution in the endothelium ? Polarity loss is typified by decreased Par3 expression ? Par3 can partially rescue lumen formation in the β1 integrin mutant     

Targeting the Cell Wall of Mycobacterium tuberculosis: Structure and Mechanism of L,D-Transpeptidase 2

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Highlights? The structure of Mtb Ldt_Mt2 shows the binding of a peptidoglycan fragment ? The structure of the complex maps the interaction between acyl donor and enzyme ? Ldts show a conserved C-terminal ykuD domain with a divergent N-terminal domain ? Based on the structure of this complex, a reaction mechanism is proposed     

Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

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Highlights? c-Src phosphorylates syndecan-4 in response to extracellular stimuli ? Syndecan-4 phosphorylation and engagement regulate Arf6 activity ? Syndecan-4-mediated Arf6 activity regulates differential integrin recycling ? Syndecan-4-mediated integrin recycling controls FA dynamics and cell migration     

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     

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     

Architecture of a dodecameric bacterial replicative helicase

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Highlights? Crystal structure of the ATPase domain of DnaB from Helicobacter pylori ? MALLS analysis shows that HpDnaB forms dodecamers ? EM reconstruction shows that HpDnaB forms head-to-head double hexamers     

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     

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     

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     

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     

A Dodecameric CcmK2 Structure Suggests β-Carboxysomal Shell Facets Have a Double-Layered Organization

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Highlights? CcmK2 shows a far stronger self-interaction than do other CcmK paralogs ? CcmK2 forms dodecamers via interactions of the αD helix on the concave face ? Hexagonally tiled CcmK2 sheets can weld via this interaction into a double layer ? FRET data supports a double-layered concave-to-concave model of the shell     

Adaptation of Aminoacyl-tRNA Synthetase Catalytic Core to Carrier Protein Aminoacylation

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Highlights? The crystal structure of the aa:CP ligase in complex with carrier protein was solved ? The interaction relies on the idiosyncratic α-helix of the aa:CP ligase ? The complex represents a unique mode of carrier protein recognition and binding ? The mechanism of amino acid attachment to carrier protein is discussed     

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     

HMGB1-Facilitated p53 DNA Binding Occurs via HMG-Box/p53 Transactivation Domain Interaction,Regulated by the Acidic Tail

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Highlights? Binding of p53 to its cognate DNA is facilitated by HMGB1 ? The N-terminal region of p53 (residues 38–61; TAD2) interacts with the HMG boxes ? The acidic tail of HMGB1 masks the p53 binding site in the free proteins ? The structure of the A-box/p53(1–93) complex shows that TAD2 acts as an ss-DNA mimic     

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     

Structure of the Catalytic Region of DNA Ligase IV in Complex with an Artemis Fragment Sheds Light on Double-Strand Break Repair

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Highlights? The crystal structure of the DNA ligase IV/Artemis complex was solved at 2.4 Å ? The structure of DNA ligase IV (residues 1–609) shows inserts ? An Artemis helix forms a three-helix bundle with two helices from DNA ligase IV ? The structure provides insights into the mutations causing LIG4 syndrome     

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