Organism-Scale Modeling of Early Drosophila Patterning via Bone Morphogenetic Proteins

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Highlights? Capturing 3D spatiotemporal content of expression data increases model utility ? Embryo geometry shapes signaling; prepatterns compensate in misshapen embryos ? Cell-surface binding proteins compensate for weak ligand/inhibitor/receptor binding ? BMP-mediated patterning is “nearly” scale-invariant     

Structure of a bacteriophytochrome and light-stimulated protomer swapping with a gene repressor

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Highlights? Bacteriophytochrome structure containing photosensory and output transducing domain ? RpBphP1 binds to the cognate repressor RpPpsR2 on illumination with far-red light ? HOS domain is distantly related to Dhp and is essential for binding to the repressor ? Light-induced protomer swapping mechanism between dimers     

Sprouty1 Regulates Reversible Quiescence of a Self-Renewing Adult Muscle Stem Cell Pool during Regeneration

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Highlights? Pax7⁺ skeletal satellite cells regenerate muscle in their endogenous environment ? Quiescent satellite cells express the RTK inhibitor Spry1 ? Spry1 is needed for satellite cells to return to quiescence after muscle injury ? Deletion of Spry1 in satellite cells depletes the muscle stem cell pool     

Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex identifies a substrate-binding channel for catalysis

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Highlights? The crystal structure of 12-lipoxygenase was solved at high resolution ? The position of an inhibitor identified the substrate binding/active site ? A channel providing access for oxygen to the active site was also discovered ? The structure accounts for virtually all features of catalysis and inhibition     

A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition

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Highlights? Splice-isoform switching favors prosurvival BCL2 family expression in human BC ? BC LSCs are quiescent and TKI-resistant in the marrow niche ? Sabutoclax, a pan-BCL2 inhibitor, enhances TKI sensitivity of bone marrow BC LSCs     

The Binding of Antibiotics in OmpF Porin

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Highlights? OmpF porin binds antibiotics in the extracellular and periplasmic pore vestibules ? MD simulations show that ionic current through OmpF is blocked by bound ampicillin ? Carbenicillin binding alters ion selectivity of OmpF but not total ionic current ? Disruption of binding increases the susceptibility of E. coli for antibiotics     

DAD2 Is an α/β Hydrolase Likely to Be Involved in the Perception of the Plant Branching Hormone,Strigolactone

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Highlights? DAD2 gene, identified by transposon tagging, encodes an α/β hydrolase fold protein ? DAD2 acts in the shoot; mutants are insensitive to strigolactones ? DAD2 crystal structure shows an internal cavity capable of binding strigolactones ? DAD2 can hydrolyze the strigolactone GR24     

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 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     

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     

The Helicobacter pylori virulence effector CagA abrogates human β-defensin 3 expression via inactivation of EGFR signaling

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Highlights? H. pylori is highly susceptible to the bactericidal activity of hBD3 ? hBD3 is initially induced by H. pylori via activation of EGFR/MAPK/JAK signaling ? H. pylori evades killing by downregulating hBD3 via CagA-mediated SHP-2 activation ? CagA virulence factor is a potent inhibitor of an immune effector mechanism     

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     

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     

Derepression of a Neuronal Inhibitor due to miRNA Dysregulation in a Schizophrenia-Related Microdeletion

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Highlights? A mouse model of a hemizygous 22q11.2 deletion shows over 50% reduction of miR-185 ? Mirta22 is a miR-185 target and a major effector of the 22q11.2 miRNA dysregulation ? Mirta22 is a prenatally biased neuronal inhibitor located in the Golgi apparatus ? Altered levels of miR-185 and Mirta22 affect dendrite and spine development     

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     

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     

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     

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