Recruitment of UBPY and ESCRT Exchange Drive HD-PTP-Dependent Sorting of EGFR to the MVB

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Highlights? HD-PTP is essential for sorting EGFR to the MVB lumen ? HD-PTP binds the ESCRT-0 subunit STAM2 at two sites ? CHMP4B and UBPY displace EGFR from ESCRT-0 and drive ESCRT-III association ? UBPY is important for sorting EGFR to the MVB lumen     

The CDK9 Tail Determines the Reaction Pathway of Positive Transcription Elongation Factor b

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Highlights? The CDK9 C-terminal tail is important for the catalytic mechanism ? CDK9 phosphorylates the CTD in a nonprocessive manner ? The CDK9 tail folds over the ATP binding site during the catalytic cycle     

Zinc Drives a Tertiary Fold in the Prion Protein with Familial Disease Mutation Sites at the Interface

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Highlights? Zinc binds to the prion protein octarepeat domain ? The zinc-bound octarepeat makes a tertiary contact to C-terminal helices 2 and 3 ? The encompassed surface carries a majority of the mutations in familial prion disease ? Familial mutations weaken this zinc-driven tertiary contact     

β-Barrel Mobility Underlies Closure of the Voltage-Dependent Anion Channel

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Highlights? The rigid N-terminal helix of VDAC stabilizes the cylindrical β-barrel ? Removal of the helix leads to elliptical, semicollapsed pore shapes ? Semicollapse can quantitatively explain conductance and selectivity of closed VDAC ? The N terminus acts as a switch controlling VDAC entry into the closed state     

Variable lymphocyte receptor recognition of the immunodominant glycoprotein of Bacillus anthracis spores

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Highlights? VLRBs use their C-terminal LRRs and the LRRCT-loop to interact with antigen ? Sequence-related VLRBs exhibit differential recognition of their BclA epitopes ? VLR4 binds a conserved protein epitope, yet is specific for B. anthracis spores     

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     

Structure of the PolIIIα-τc-DNA Complex Suggests an Atomic Model of the Replisome

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Highlights? Crystal structure of the DNA polymerase IIIα in complex with τ_c and a DNA substrate ? τ_c interacts with the C-terminal domain of PolIIIα through its C-terminal helix and the loop that follows it ? PolIIIα in complex with τ_c and DNA displays an open form ? The structure of this complex suggests an atomic model of the bacterial replisome     

The Molecular Basis for Substrate Specificity of the Nuclear NIPP1:PP1 Holoenzyme

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Highlights? The first structure of a nuclear PP1 holoenzyme, NIPP1:PP1 ? The NIPP1 helix defines a unique interaction site on PP1 ? Identification of a common PP1-binding pocket, the ΦΦ motif-binding pocket ? Explains the mechanism of nuclear substrate selection by PP1     

Incoming RNA Virus Nucleocapsids Containing a 5′-Triphosphorylated Genome Activate RIG-I and Antiviral Signaling

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Highlights? RIG-I is activated by the incoming RNA virus nucleocapsids during infection ? RIG-I activation requires a 5′triphosphate dsRNA structure on the nucleocapsids ? Viral nucleocapsids trigger conformational switching and oligomerization of RIG-I ? RIG-I directly binds to viral nucleocapsids containing a 5′triphosphate dsRNA structure     

The E3 Ligase Parkin Maintains Mitochondrial Integrity by Increasing Linear Ubiquitination of NEMO

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Highlights? The stress-protective prosurvival activity of parkin depends on NEMO ? Parkin binds to LUBAC and increases linear ubiquitination of NEMO ? OPA1 is upregulated via parkin/NEMO/NF-κB for maintaining mitochondrial integrity ? TNF-α signaling via NEMO/NF-κB is impaired in parkin-deficient cells     

Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation

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Highlights? Fbxl10 binds to most CpG islands in ESCs ? Fbxl10 recruits Nspc1 and Ring1B to CpG islands ? The Fbxl10, Nspc1, and Ring1B complex is required for H2A monoubiquitylation ? Fbxl10 is required for proper ESC differentiation     

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     

Crystal structures of a stabilized β1-adrenoceptor bound to the biased agonists bucindolol and carvedilol

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Highlights? Structures of β1AR bound to the biased agonists bucindololol and carvedilol ? The biased agonists form unique contacts with β1AR not seen with other antagonists ? The structures explain the pharmacological differences in the Arg389Gly polymorphism     

β-Catenin-Driven Binary Fate Specification Segregates Germ Layers in Ascidian Embryos

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Highlights? β-catenin nuclear asymmetry after animal-vegetal-oriented cell divisions ? β-catenin nuclear asymmetry drives binary cell fate choices ? Combinatorial codes of nuclear β-catenin activation segregate ascidian germ layers ? Nuclear β-catenin ON-to-OFF activity is required for marginal mesoderm formation     

Phage pierces the host cell membrane with the iron-loaded spike

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Highlights? Phage tails and other contractile injection systems contain a central spike protein ? The tip of the spike is “hardened” by a centrally positioned iron ion ? The spike appears to pierce the host cell membrane without unfolding ? An OB-fold with an extra β-hairpin is a conserved feature of all central spikes     

The Microtubule-Binding Protein Ensconsin Is an Essential Cofactor of Kinesin-1

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Highlights? Ensconsin is required for cargo transport driven by kinesin-1 ? The C terminus of ensconsin activates kinesin-1; its N terminus binds microtubules ? Kinesin-1 mutants without autoinhibitory activity do not require ensconsin     

Structure of the MST4 in Complex with MO25 Provides Insights into Its Activation Mechanism

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Highlights? MO25 forms a stable complex with MST4 to enhance its kinase activity ? Association of MO25 activates MST4 by rotating its αC helix to active conformation ? Kinase-domain-mediated dimerization is required for MST4 trans-autophosphorylation ? MO25-stimulated activation of MST4 promotes apoptosis in HEK293T cells     

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     

POT1-TPP1 Regulates Telomeric Overhang Structural Dynamics

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Highlights? POT1 binds the telomere overhang sequentially one OB fold at a time ? POT1 binding exhibits 3′ to 5′ directionality ? POT1-TPP1N induces dynamic folding and unfolding of telomeric overhang ? POT1-TPP1N slides back and forth on the telomeric overhang