3ebm

Crystal structure of human translationally controlled tumour associated protein (hTCTP) mutant E12V

spinqualitylabelsall models 3ebm, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ebm 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. Method: X-ray diffraction, Resolution 2.6Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TCTP_HUMAN Involved in calcium binding and microtubule stabilization. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Ras homolog enriched in brain (Rheb), a small GTPase, positively regulates the mTORC1 pathway. The GDP-GTP exchange of Rheb has been suggested to be facilitated by translationally controlled tumor protein (TCTP). Here we demonstrate that human TCTP (hTCTP) interacts with human Rheb (hRheb) and accelerates its GDP release in vitro and that hTCTP activates the mTORC1 pathway in vivo. To investigate the underlying mechanism, we built structure models of GDP- and GTP-bound hRheb in complexes with hTCTP and performed molecular dynamics simulations of the models, which predict key residues involved in the interactions and region of hRheb undergoing conformational change during the GDP-GTP exchange. These results are verified with site-directed mutagenesis and in vitro biochemical and in vivo cell biological analyses. Furthermore, a crystal structure of the E12V mutant hTCTP, which lacks the guanine nucleotide exchange factor activity, shows that the deficiency appears to be caused by loss of a salt-bridging interaction with Lys-45 of hRheb. These data collectively provide insights into the molecular mechanisms of how hTCTP interacts with hRheb and activates the mTORC1 pathway. Molecular basis of the acceleration of the GDP-GTP exchange of human ras homolog enriched in brain by human translationally controlled tumor protein.,Dong X, Yang B, Li Y, Zhong C, Ding J J Biol Chem. 2009 Aug 28;284(35):23754-64. Epub 2009 Jul 1. PMID:19570981 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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