The Crystal Structure of the Catalytic Domain of the NF-κB Inducing Kinase Reveals a Narrow but Flexible Active Site

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Highlights? Production of soluble NIK kinase domain ? Structures of apo murine and human NIK possess active conformation ? Structure of mNIK bound to inhibitors reveals conformational flexibility ? Inhibitor potency varies against mNIK and hNIK due to substitution in the active site     

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     

LSD2/KDM1B and Its Cofactor NPAC/GLYR1 Endow a Structural and Molecular Model for Regulation of H3K4 Demethylation

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Highlights? Identifying NPAC as a novel LSD2 cofactor stimulating H3K4 demethylation ? Structure determination of LSD2 alone or in complex with NPAC and histone H3 peptide ? Defining the key NPAC residues essential for its intrinsic LSD2 cofactor activity ? Establishing a molecular model for how a cofactor regulates histone demethylation     

Molecular Organization and ATP-Induced Conformational Changes of ABCA4, the Photoreceptor-Specific ABC Transporter

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Highlights? Structure of ABCA4 was determined by electron microscopy to a resolution of 18 Å ? Binding of ATP induced conformational changes in cytoplasmic and transmembrane regions ? Transport mechanism is proposed based on EM and hydrogen/deuterium exchange data     

Crystal Structure and Mechanism of Activation of TANK-Binding Kinase 1

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Highlights? X-ray crystal structures of active and inactive human TBK1 kinase ? Structure in complex with specific inhibitors shows binding preferences ? The CTD is fully extended and constitutively interacts with adaptors ? Dimerization is required for kinase activation but not activity     

Structure and Mechanism of a Nitrate Transporter

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Highlights? Structure of the nitrate transporter NarU in substrate-free and -bound states ? Distinct conformations of NarU in substrate-free and -bound states ? Identification of a substrate binding site and transport path ? Transport mechanism may deviate from the rocker-switch model     

Structure of a Pestivirus Envelope Glycoprotein E2 Clarifies Its Role in Cell Entry

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Highlights? Structure of the major antigenically dominant protein of BVDV ? The overall fold of BVDV E2 shows no similarity to the class II fusion proteins ? At low pH, BVDV E2 N-terminal domain is disordered ? Entry mechanism of BVDV is probably applicable to hepatitis C virus     

Structure and Ubiquitination-Dependent Activation of TANK-Binding Kinase 1

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Highlights? TBK1 forms a dimer structurally distinct from IKKβ ? Structure of TBK1 with inhibitors reveals basis for specific inhibition ? TBK1 is K63 polyubiquitinated on Lys30 in the kinase domain and Lys401 in the scaffold/dimerization domain ? K63-linked ubiquitination of dimerized TBK1 is required for kinase activation and signaling     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

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Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11     

Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration

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Highlights? Not all hepatocytes undergo cell division during liver regeneration ? Hypertrophy precedes proliferation in the regenerating liver ? Hepatocytes infrequently enter into M phase during liver regeneration ? Binuclear hepatocytes undergo cell division to generate mononuclear hepatocytes     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

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     

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     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

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Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia