HnRNP L and HnRNP A1 Induce Extended U1 snRNA Interactions with an Exon to Repress Spliceosome Assembly

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Highlights? HnRNP L recruits hnRNP A1 and U1 snRNA to sequences upstream of the 5′ splice site ? HnRNP L-induced extended base pairing of U1 snRNA inhibits exchange for U6 snRNA ? Local traps in spliceosome assembly are naturally exploited mechanisms of regulation ? Extended base pairing of U1 may account for much of regulation by hnRNPs L and A1     

DOLORS: Versatile Strategy for Internal Labeling and Domain Localization in Electron Microscopy

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Highlights? DOLORS is a strategy for EM labeling using AviTag and streptavidin ? Internal domains within a large protein can be labeled and identified ? Higher accuracy and precision are achieved by sampling multiple RCT reconstructions ? Offers a powerful method for deciphering moderate-resolution EM structures     

Decision Making during the Psychological Refractory Period

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Highlights? The PRP interferes with decision making and routing to the motor response ? Sensory evidence accumulation can occur for multiple decisions at the same time ? A large fraction of the PRP occurs after the commitment to a choice ? Evidence accumulation and sensory-motor mapping are distinct processes     

Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy

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Highlights? We have determined the cryo-EM structures of ORC, ORC-DNA, and ORC-Cdc6-DNA ? We show that ORC is arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to Orc2 ? DNA and Cdc6 binding causes large conformational changes in ORC ? Origin DNA is proposed to bind to the interior surface of the crescent-shaped ORC     

Functional implications from the Cid1 poly(U) polymerase crystal structure

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Highlights? Our structure identifies the UTP-binding pocket of the Cid1 protein ? The atomic model suggests a central role for the helix 4 ? We suggest that the NRM loop is blocked after triphosphate recognition ? We identify several loops likely involved in the RNA primer association/stabilization     

Unfolded phosphopolypeptides enable soft and hard tissues to coexist in the same organism with relative ease

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Highlights? Some unfolded phosphoproteins form stable complexes with amorphous calcium phosphate. ? Stable complexes require ≥3 phosphorylated residues within a short sub-sequence. ? Soft and hard tissues can co-exist in the same organism because of these complexes.     

Spatial restriction of bone morphogenetic protein signaling in mouse gastrula through the mVam2-dependent endocytic pathway

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Highlights? mVam2 mediates endocytic transport from late endosomes to lysosomes ? mVam2 is essential for assembly of large apical vacuoles in visceral endoderm ? Loss of mVam2 results in hyperactivation of BMP signaling ? The mVam2-dependent BMP attenuation contributes to patterning in gastrulation     

Unilateral Dampening of Bmp Activity by Nodal Generates Cardiac Left-Right Asymmetry

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Highlights? Cardiac laterality involves Nodal modulating an antimotogenic Bmp activity ? The Nodal target Hyaluronan synthase 2 unilaterally dampens Bmp signaling activity ? Nonmuscle myosin II is positively regulated by Bmp within cardiac tissue ? High levels of nonmuscle myosin II activity reduce cardiac cell motility     

A Predictive Computational Model of the Dynamic 3D Interphase Yeast Nucleus

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Highlights? We describe a predictive computational model of dynamic chromosomes in the yeast nucleus ? The model quantitatively recapitulates experimental data on nuclear organization ? The model predicts nuclear reorganization in response to treatment by rapamycin ? Large-scale nuclear organization is dominated by unspecific effects of crowded polymers     

Functional Classification of Immune Regulatory Proteins

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Highlights? An intermediate sequence based clustering algorithm, Brotherhood, is introduced ? The Brotherhood method is used to assign functional families within the human IgSF ? Newly annotated nectin-like family member, CRTAM, structure is solved ? Homophilic transinteraction is observed for CRTAM     

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     

Promiscuous Interactions of gp78 E3 Ligase CUE Domain with Polyubiquitin Chains

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Highlights? The ubiquitin ligase gp78 recruits ubiquitinated substrates via its CUE domain ? gp78CUE:Ub complex reveals a large set of specific interactions ? gp78CUE binds to both distal and proximal moities of diubiquitin in a similar fashion ? The gp78CUE domain binds to K48- and K63-linked diubiquitin equally well     

MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

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Highlights? Satellite cells can differentiate into brown adipocytes ? MicroRNA-133 targets Prdm16 3′UTR and controls brown adipose determination ? MicroRNA-133 antagonism induces active brown adipocytes within regenerating muscle ? MicroRNA-133 antagonism impedes the development of obesity     

Information encoded in non-native States drives substrate-chaperone pairing

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Highlights? In vitro refolding intermediates are aptly targeted to specific chaperones ? Substrate-chaperone pairing depends on their relative affinity ? Structure of the intermediates play crucial role in precise chaperone targeting ? Substrates may be mistargeted due to large alterations in chaperone molar ratios     

Out but Not In: The Large Transmembrane β-Barrel Protein FhuA Unfolds but Cannot Refold via β-Hairpins

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Highlights? Mechanical un- and refolding studies of single large transmembrane β-barrel proteins ? FhuA unfolds via highly reproducible steps formed by single β-hairpins ? Once unfolded, FhuA folds into highly irreproducible structures ? To assist folding into the membrane, FhuA may require cofactors     

ATP-Driven Remodeling of the Linker Domain in the Dynein Motor

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Highlights? Structural changes in axonemal and cytoplasmic dynein motors seen by cryo-EM ? Movement is amplified by a hinge action within dynein's linker domain ? The linker is a stable structure that is actively remodeled by dynein's AAA+ modules ? Dynein's neck subdomain interacts with AAA4 and is an intrinsic site of flexibility     

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     

The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation

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Highlights? Ell3 is preferentially found at active, poised, and inactive enhancers in ES cells ? Promoter-proximal Pol II occupancy at key developmental genes requires Ell3 ? Cohesin functions in Ell3-associated enhancer-promoter communication ? Recruitment of P-TEFb within SEC during differentiation is Ell3 dependent     

Structural basis for substrate targeting and catalysis by fungal polysaccharide monooxygenases

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Highlights? 1.1/1.37 Å polysaccharide monooxygenases structures have active-site dioxygen species ? The structures reveal a large variance in substrate binding surfaces ? Proposed electron transport pathways in polysaccharide monooxygenases are conserved ? Polysaccharide monooxygenases and CBM₃₃ enzymes likely bind substrates differently