Structural Basis for the Versatile Interactions of Smad7 with Regulator WW Domains in TGF-β Pathways

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Highlights? HECT ubiquitin ligases and YAP use single or multiple WW domains to select Smad protein targets ? The targets can require multiple binding sites (R-Smads) or unique sites (ISmads) ? Binding sites are phosphorylation dependent (R-Smads) or independent (ISmad) ? Smurf1 WW1-homodimers can stabilize the close and inactive conformation of the ligase     

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     

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     

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     

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     

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     

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     

Cotranslational Response to Proteotoxic Stress by Elongation Pausing of Ribosomes

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Highlights? Proteotoxic stress reduces global protein synthesis by influencing elongation ? Proteotoxic stress induces ribosome pausing on mRNAs in the first 50 codons ? Molecular chaperones facilitate translation elongation by binding to nascent chains ? Ribosomes fine tune elongation rate in response to proteotoxic stress     

The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation

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Highlights? Fast motion interconverts states with significant conformational entropy. ? Fast internal motion can be characterized in a site resolved way using solution NMR relaxation phenomena. ? Internal protein motion can be used as a proxy for conformational entropy. ? Conformational entropy can contribute significantly to ligand binding by proteins.     

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     

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     

Selective and specific inhibition of the plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin

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Highlights? The fungal secondary metabolite Cladosporin inhibits liver- and blood-stage malaria parasites ? Cladosporin specifically targets lysyl-tRNA synthetase (Krs1) ? Cladosporin is >100-fold more potent against parasite Krs1 relative to the human enzyme ? Two amino acids in the Krs1 ATP-binding pocket confer species-selective inhibition     

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     

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     

The Mitochondrial RNA-Binding Protein GRSF1 Localizes to RNA Granules and Is Required for Posttranscriptional Mitochondrial Gene Expression

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Highlights? GRSF1 (G-rich sequence binding factor 1) is a mitochondrial RNA-binding protein ? GRSF1 localizes to granules containing newly synthesized RNA in close proximity to mitochondrial nucleoids ? GRSF1 specifically binds one mRNA and two long noncoding RNAs transcribed from contiguous genes on the light strand of mtDNA ? Loss of GRSF1 leads to misloading of RNAs onto the mitochondrial ribosome and a specific translation defect