RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor

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Highlights? Crystal structures of the cytokine-binding regions of OPG and RANK bound to RANKL ? High-affinity OPG engagement is associated with a distinct RANKL-binding cleft ? Structural basis of how the OPG^F96L mutation promotes juvenile Paget’s disease     

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

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Highlights? Snx3 is highly expressed in vertebrate hematopoietic tissues ? Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates ? Snx3 and Vps35 physically interact with Tfrc ? Snx3 is required for endosomal recycling of Tf-Tfrc complex     

Anions Mediate Ligand Binding in Adineta vaga Glutamate Receptor Ion Channels

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Highlights? The AvGluR1 LBD is a hybrid structure with iGluR prokaryotic and eukaryotic features ? AvGluR1 binds hydrophobic amino acids as well as glutamate ? Chloride ions acts as surrogate ligand atoms in the Ala, Ser, and Met complexes ? The AvGluR1 LBD assembles as a dimer but with very low affinity     

The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis

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Highlights? Bcl6 is a critical antiatherogenic regulator ? Inhibition of Bcl6-SMRT/NCoR interactions induces atherogenic gene expression ? SMRT and NCoR cistromes each exceed 30,000 sites, with a nearly 50% overlap ? Bcl6 recruits SMRT and NCoR to NF-κB-driven inflammatory and tissue remodeling genes     

Insights into Negative Regulation by the Glucocorticoid Receptor from Genome-wide Profiling of Inflammatory Cistromes

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Highlights? TLR4 activation dramatically remodels the GR cistrome in macrophages ? Both negative and positive GR enhancers include GREs, NF-κB, and AP-1 sites ? Classical models fail to predict positive or negative polarity of GR regulation ? Hormone treatment marks negative enhancers by histone deacetylation     

Identification of the Outer-Inner Dynein Linker as a Hub Controller for Axonemal Dynein Activities

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Highlights? Outer dynein intermediate chain 2 (IC2) forms the outer-inner dynein (OID) linker ? A mutation to IC2 nonspecifically activates the outer dynein activity ? The mutation to IC2 alters the inner-dynein-dependent flagellar waveform ? The OID linker regulates flagellar beating by controlling outer and inner dyneins     

Human IL-34 and CSF-1 Establish Structurally Similar Extracellular Assemblies with Their Common Hematopoietic Receptor

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Highlights? Structural insights into the complete extracellular human IL-34:CSF-1R complex ? The C-terminal tail of hIL-34 is flexible and heavily O-linked glycosylated ? Inclusion of N-linked glycans drastically improves fitting of models to SAXS data ? Consensus principles for hCSF-1R activation by its two distinct cytokine ligands     

Functional Insights from the Crystal Structure of the N-Terminal Domain of the Prototypical Toll Receptor

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Highlights? The N-terminal cap of Toll adopts a new fold ? It resembles a duplicated beta hairpin structure with three disulphide bonds ? Toll LRRNT cap is not critical for Spätzle binding ? The first 13 LRRs are sufficient for Spätzle binding     

Dynamic Interaction between Sigma-1 Receptor and Kv1.2 Shapes Neuronal and Behavioral Responses to Cocaine

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Highlights? Sig-1R activity enhances sensitivity to cocaine by decreasing accumbal firing ? Cocaine decreases accumbal firing via Sig-1R-dependent increase of Kv1.2 current ? The Sig-1R forms a complex with Kv1.2 channel in the nucleus accumbens shell ? Cocaine triggers a long-lasting upregulation of the Sig-1R-Kv1.2 channel complex     

ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility

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Highlights? ALKBH5 is a mammalian m⁶A RNA demethylase ? RNA demethylation affects mRNA export and RNA metabolism ? RNA demethylation is important for mouse fertility ? Reversible mammalian messenger RNA methylation affects gene expression     

The Tripartite Motif Protein MADD-2 Functions with the Receptor UNC-40 (DCC) in Netrin-Mediated Axon Attraction and Branching

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Highlights? UNC-6 (Netrin), its receptor UNC-40 (DCC), and the TRIM protein MADD-2 promote axon branching ? MADD-2 and UNC-40 proteins are localized to the affected axon branch ? MADD-2 stimulates axon attraction to Netrin by acting as an UNC-40 cofactor ? MADD-2 enables UNC-40 to recruit MIG-10, an actin-binding effector protein     

Conformational Dynamics of the Rpt6 ATPase in Proteasome Assembly and Rpn14 Binding

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Highlights? Proteasome ATPase Rpt6 undergoes helix-coil exchange in its C-terminal domain ? Rpt6 G^360,387A has a stabilized four-helix bundle and raised melting temperature ? Assembly chaperone Rpn14 binds selectively to the four-helix bundle Rpt6 conformer ? Rpt6 G^360,387A (rpt6AA) is synthetically defective with an rpn14 null mutation     

Epigenetic Regulation of miR-184 by MBD1 Governs Neural Stem Cell Proliferation and Differentiation

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Highlights? MBD1 governs the proliferation and differentiation of neural stem cells (NSCs) ? MBD1 controls the expression of miRNAs, including miR-184, in NSCs ? MiR-184 represses the expression of Numblike ? Numblike rescues the effects of abnormal MBD1 and miR-184 expression     

Redox-Dependent Control of FOXO/DAF-16 by Transportin-1

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Highlights? FOXO forms redox-sensitive, disulfide-dependent complexes with several proteins ? Transportin-1 binds to FOXO via a disulfide and regulates its nuclear localization ? Redox and insulin signaling govern FOXO nuclear localization via distinct pathways ? Redox control of longevity protein FOXO/DAF-16 is evolutionarily conserved     

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     

Correction of both NBD1 energetics and domain interface is required to restore ΔF508 CFTR folding and function

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Highlights? NBD1 and NBD1-CL4 interface instability limit CFTR conformational maturation ? ΔF508 mutation thermodynamically and kinetically destabilizes NBD1 ? Stabilization of ΔF508-NBD1 is insufficient for CFTR-coupled domain folding ? ΔF508 CFTR folding and function require both NBD1 and NBD1-CL4 stabilization     

Moderation of Arabidopsis Root Stemness by CLAVATA1 and ARABIDOPSIS CRINKLY4 Receptor Kinase Complexes

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Highlights? CLV1 receptor kinase regulates stemness in Arabidopsis root and shoot meristems ? CLV1 and ACR4 form homo- and heteromeric complexes as shown by a novel FRET assay ? CLV1/ACR4 complexes differ in composition between plasma membrane and plasmodesmata ? CLV1/ACR4 complexes regulate distal root meristem maintenance     

Endogenous Purification Reveals GREB1 as a Key Estrogen Receptor Regulatory Factor

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Highlights? A proteomic method identifies protein-protein interaction in primary tumors ? GREB1 is the top estrogen-induced ER-interacting protein ? GREB1 is an essential ER cofactor recruited to chromatin ? GREB1 is an independent prognostic marker