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     

Repeated Origin of Three-Dimensional Leaf Venation Releases Constraints on the Evolution of Succulence in Plants

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Highlights? The evolution of extreme succulence in leaves is constrained by low vein density ? An unusual 3D leaf venation has evolved repeatedly in the most succulent leaves ? 3D leaves maintain veins in close proximity to photosynthetic tissues ? 3D venation facilitates the evolution of previously inaccessible phenotypes     

Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling

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Highlights? Supernumerary centrosomes nucleate cilia, resulting in superciliated cells (SCC) ? Ciliary proteins are reduced in concentration in SCC, compromising signaling ? Presence of extra cilia disrupts epithelial organization in 3D spheroid culture ? Extra cilia may contribute to disease phenotypes by disrupting signaling     

A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation,CHK1 Activation,and DNA Repair

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Highlights? BRCA1 E3 ligase activity is essential for a subset of DNA damage responses ? BRCA1 V26A mutant cells are sensitive to topoisomerase inhibitors but not mitomycin C ? BRCA1 selectively ubiquitylates claspin after topoisomerase inhibition ? BRCA1 E3 ligase inactivation selectively impairs CHK1 activation     

Crystal structures of Aureochrome1 LOV suggest new design strategies for optogenetics

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Highlights? Crystal structures in dark and light states determined for Aureochrome1 LOV ? Significant light induced change observed in F298 and quaternary structure ? Potential photocycle mutant variants, altering the light-state lifetime, identified ? Possible mechanism of signaling in topologically unique Aureo1 speculated     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

The structural basis for tight control of PP2A methylation and function by LCMT-1

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Highlights? LCMT-1 makes extensive contacts to PP2A active site for methylation of PP2A tail ? PP2A methylation is stimulated by phosphatase activation, hampered by inactivation ? LCMT-1 would facilitate efficient transition of activated PP2A to holoenzymes ? A high-affinity dnLCMT-1 mutant attenuates the cell cycle without causing cell death     

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     

The structure of dimeric apolipoprotein A-IV and its mechanism of self-association

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Highlights? Structure of dimeric apoA-IV solved to 2.4 Å by X-ray crystallography ? Structure confirmed through biochemical and mutational analysis ? Understanding of apoA-IV dimerization allowed us to create a monomeric mutant ? Structural features in the dimer offer clues to the genesis of apoA-IV lipoproteins     

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     

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     

Microtubules Enable the Planar Cell Polarity of Airway Cilia

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Highlights? PCP proteins are asymmetric at apical junctions in the airways before ciliogenesis ? PCP protein asymmetry and cilium orientation emerge gradually during development ? Cilium misorientation correlates with loss of PCP protein asymmetry in PCP mutants ? Microtubules appear to organize cilium orientation and PCP protein asymmetry     

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     

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     

The WW Domain Protein Kibra Acts Upstream of Hippo in Drosophila

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Highlights? The WW domain protein Kibra is a Hippo signalling component ? Kibra restricts organ size via Yorkie and acts upstream of Hippo and Merlin ? Kibra synergizes with Expanded and binds to Merlin     

Malaria Parasites Co-opt Human Factor H to Prevent Complement-Mediated Lysis in the Mosquito Midgut

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Highlights? Malaria gametes evade human complement by binding factor H ? The plasmodial protein PfGAP50 binds to factor H on the gamete surface ? Binding of factor H results in inactivation of the complement protein C3b ? Functional inhibition of factor H or PfGAP50 reduces parasite transmission to the mosquito