1r5l
From Proteopedia
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Crystal Structure of Human Alpha-Tocopherol Transfer Protein Bound to its Ligand
Contents |
Overview
Human alpha-tocopherol (alpha-T) transfer protein (ATTP) plays a central, role in vitamin E homeostasis, preventing degradation of alpha-T by, routing this lipophilic molecule for secretion by hepatocytes. Mutations, in the gene encoding ATTP have been shown to cause a severe deficiency in, alpha-T, which results in a progressive neurodegenerative spinocerebellar, ataxia, known as ataxia with vitamin E deficiency (AVED). We have, determined the high-resolution crystal structure of human ATTP with, (2R,4'R,8'R)-alpha-T in the binding pocket. Surprisingly, the ligand is, sequestered deep in the hydrophobic core of the protein, implicating a, large structural rearrangement for the entry and release of alpha-T. A, comparison to the structure of a related protein, Sec14p, crystallized, without a bona fide ligand, shows a possibly relevant open conformation, for this family of proteins. Furthermore, of the known mutations that, cause AVED, one mutation, L183P, is located directly in the binding, pocket. Finally, three mutations associated with AVED involve arginine, residues that are grouped together on the surface of ATTP. We propose that, this positively charged surface may serve to orient an interacting, protein, which might function to regulate the release of alpha-T through, an induced change in conformation of ATTP.
Disease
Known disease associated with this structure: Ataxia with isolated vitamin E deficiency OMIM:[600415]
About this Structure
1R5L is a Single protein structure of sequence from Homo sapiens with VIV as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency., Min KC, Kovall RA, Hendrickson WA, Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14713-8. Epub 2003 Dec 1. PMID:14657365
Page seeded by OCA on Mon Nov 12 19:00:31 2007
