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     

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     

Mixed-Linkage Ubiquitin Chains Send Mixed Messages

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Highlights? K48 and K63 linkages in branched and unbranched tri-Ub retain their structural features ? Linkage-selective receptors recognize K48 and K63 linkages in the branched tri-Ub ? Linkage-specific deubiquitinases cleave their cognate Ub-Ub linkages in the mixed-linkage chains ? The 26S proteasome recognizes and processes branched K48- and K63-linked tri-Ub     

ZNF750 is a p63 target gene that induces KLF4 to drive terminal epidermal differentiation

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Highlights? Induction of ZNF750 expression is necessary for terminal epidermal differentiation ? The C2H2 domain of ZNF750 is necessary for its prodifferentiation function ? p63 is necessary for the induction of ZNF750 expression during differentiation ? ZNF750 activates the expression of KLF4 to drive differentiation gene expression     

The n-SET Domain of Set1 Regulates H2B Ubiquitylation-Dependent H3K4 Methylation

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Highlights? H2B ubiquitylation directly stimulates H3K4 methylation by the yeast Set1 complex ? Swd2 is not directly required for the H3K4 methylation activity of the yeast Set1 complex ? The Set1 n-SET domain plays a critical role in H2Bub-dependent H3K4 methylation ? Spp1 is conditionally involved in n-SET- and H2Bub-dependent H3K4 methylation     

c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-β Type II Receptor

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Highlights? c-Cbl is a NEDD8 E3 ligase of TβRII ? c-Cbl neddylates TβRII at Lys556 and Lys567 ? Neddylation stabilizes TβRII by regulating receptor endocytic routes ? Aberrant neddylation of TβRII is associated with leukemia     

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     

Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages

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Highlights? M. tuberculosis permeabilizes phagosomes and activates cytosolic signaling pathways ? Host cytoplasmic DNA receptors sense M. tuberculosis extracellular DNA ? DNA recognition activates the STING/TBK1/IRF3 pathway ? Cytosolic sensing promotes M. tuberculosis infection     

IKKε-Mediated Tumorigenesis Requires K63-Linked Polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 Ubiquitin Ligase Complex

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Highlights? K63-linked ubiquitination regulates IKKε innate immune and oncogenic functions ? IKKε is ubiquitinated on K30, K401, and K416 ? Ubiquitination of K30 and K401 is essential for IKKε activity and oncogene function ? A cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex binds to and modifies IKKε     

Structural and functional analysis of HtrA1 and its subdomains

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Highlights? IGFBP-like domain structure suggests that it is incompetent for IGF binding ? Kazal-like domain structure shows distorted “P1” loop incompetent for inhibition ? Protease domain shows catalytic readiness in apo form ? SAXS envelope for full-length HtrA1     

Structure and Dynamics of the Second CARD of Human RIG-I Provide Mechanistic Insights into Regulation of RIG-I Activation

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Highlights? The structure of a CARD of human RIG-I ? The mechanism and structural role of phosphorylation are revealed ? In trans interaction with the Helicase and regulatory domains is shown ? Lys172 lies in proximity to the CARD2:helicase-CTD interface     

Legionella pneumophila Effector RomA Uniquely Modifies Host Chromatin to Repress Gene Expression and Promote Intracellular Bacterial Replication

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Highlights? Upon infection, L. pneumophila secretes RomA, a SET domain-containing methyltransferase ? RomA triggers H3K14 trimethylation, causing a switch from gene activation to repression ? ChIP-seq identified 4,870 H3K14 methylated promoter regions, including innate immune genes ? RomA SET domain is required for efficient intracellular replication of L. pneumophila     

OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme function

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Highlights? Identification of OTUB1 mutants with impaired ability to inhibit E2 enzymes ? Crystal structure of a ubiquitin-charged E2 bound to OTUB1 ? Molecular basis of Lys48-linked ubiquitin chain recognition by OTUB1 determined ? OTUB1 employs product inhibition mimicry to inhibit E2 enzymes     

Structure of a bacteriophytochrome and light-stimulated protomer swapping with a gene repressor

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Highlights? Bacteriophytochrome structure containing photosensory and output transducing domain ? RpBphP1 binds to the cognate repressor RpPpsR2 on illumination with far-red light ? HOS domain is distantly related to Dhp and is essential for binding to the repressor ? Light-induced protomer swapping mechanism between dimers     

Myosin-IXA regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions

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Highlights? Myosin-IXA, an actin-motor- and RhoGAP-protein, is required for collective migration ? Myosin-IXA is required for radial actin bundle assembly at nascent cell-cell contacts ? The localization of myosin-IXA to actin bundles is dependent on its motor domain ? Myosin-IXA RhoGAP domain locally inhibits Rho stabilizing nascent cell-cell contacts     

Homeodomain-interacting protein kinase regulates yorkie activity to promote tissue growth

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Highlights? Hipk induces tissues overgrowth and leads to activation of Yki target genes ? Hipk is required for activity of hyperactive Yki ? Hipk kinase function is essential to promote Yki target genes     

The Structure of the Tiam1 PDZ Domain/ Phospho-Syndecan1 Complex Reveals a Ligand Conformation that Modulates Protein Dynamics

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Highlights? The Tiam1 PDZ domain preferentially binds a subset of syndecan (SDC) proteins ? The PDZ domain/phospho-SDC1 structure reveals a phosphoryl binding pocket ? Ligand specificity and phosphorylation regulate PDZ/SDC interactions and signaling ? Tiam1 PDZ domain dynamics are ligand-dependent and regulated by phosphorylation     

Posttranslational acetylation of α-tubulin constrains protofilament number in native microtubules

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Highlights? α-TAT mutants have short microtubules and variable protofilament number ? α-tubulin K40 acetylation promotes interprotofilament salt bridges ? α-tubulin K40 acetylation is a key constraint on protofilament number in vivo     

Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCι in complex with a substrate peptide from Par-3

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Highlights? The 3D structure of PKCι in complex with a peptide from Par-3 is determined ? PKCι does not need phosphorylation of Thr402 in its activation loop for its activity ? aPKCs do not need a priming kinase for their activations ? The PKCι/Par-3 structure reveals a unique substrate recognition patterns for aPKCs     

Loss of Rb Cooperates with Ras to Drive Oncogenic Growth in Mammalian Cells

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Highlights? Oncogenic Ras drives weak growth through the PI3K canonical growth pathway ? A novel E2F-independent role for the Rb family in cell biogenesis ? Ras and loss of Rb synergize to give robust and sustained cell growth ? PI3K pathway is crucial for sustained growth, acting to maintain nutrient uptake