4emo

Crystal structure of the PH domain of SHARPIN

spinqualitylabelsall models 4emo, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4emo is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SHRPN_HUMAN] Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Publication Abstract from PubMed E3 ubiquitin ligase complex called LUBAC (linear ubiquitin chain assembly complex) that catalyses the formation of linear ubiquitin chains and regulates immune and apoptopic signalling pathways. The C-terminal half of SHARPIN contains ubiquitin like domain (UBL) and Npl4-zinc finger (NZF) domains that mediate the interaction with the LUBAC subunit HOIP and ubiquitin, respectively. In contrast, the N-terminal region does not show any homology with known protein interaction domains but has been suggested to be responsible for self-association of SHARPIN, presumably via a coiled-coil region. We have determined the crystal structure of the N-terminal portion of SHARPIN, which adopts the highly conserved pleckstrin homology (PH) superfold that is often used as a scaffold to create protein interaction modules. We show that in SHARPIN this domain does not appear to be used as a ligand recognition domain since it lacks many of the surface properties that are present in other PH fold-based interaction modules. Instead it acts as a dimerization module extending the functional applications of this superfold. Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold.,Stieglitz B, Haire LF, Dikic I, Rittinger K J Biol Chem. 2012 May 1. PMID:22549881 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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