3msh

Crystal structure of Hepatitis B X-Interacting Protein at high resolution

spinqualitylabelsall models 3msh, resolution 1.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3msh is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.51Å Ligands: GOL, IPA, PG4, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LTOR5_HUMAN As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway. Down-regulates hepatitis B virus (HBV) replication. Publication Abstract from PubMed Hepatitis B X-interacting protein (HBXIP) is a ubiquitous protein that was originally identified as a binding partner of the hepatitis B viral protein HBx. HBXIP is also thought to serve as an anti-apoptotic cofactor of survivin, promoting the suppression of pro-caspase-9 activation. Here were port the crystal structure of the shortest isoform of HBXIP (91 aa long, approximately 11 kDa) at 1.5 A resolution. HBXIP crystal shows a monomer per asymmetric unit, with a profilin-like fold which is common to a super family of proteins, the Roadblock/LC7 domain family involved in protein-protein interactions. Based on this fold, we propose that HBXIP can form a dimer that can indeed be found in the crystal when symmetric molecules are generated around the asymmetric unit. This dimer shows an extended beta-sheet area formed by 10 anti-parallel beta-strands from both subunits. Another interesting aspect of the proposed HBXIP dimer interface is the presence of a small leucine zipper between the two alpha2 helices of each monomer. In solution, the scattering curve obtained by small-angle X-ray scattering for the sample used for crystallization indicates that the protein is dimeric form in solution. The fit between the experimental small angle X-ray scattering curve and the back calculated curves for two potential crystal dimers shows a significant preference for the Roadblock/LC7 fold dimer model. Moreover, the HBXIP crystal structure represents a step towards understanding the cellular role of HBXIP. Structural characterization of HBXIP: the protein that interacts with the anti-apoptotic protein survivin and the oncogenic viral protein HBx.,Garcia-Saez I, Lacroix FB, Blot D, Gabel F, Skoufias DA J Mol Biol. 2011 Jan 14;405(2):331-40. Epub 2010 Nov 6. PMID:21059355 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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