1x7t
From Proteopedia
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Structure of TTR R104H: a non-amyloidogenic variant with protective clinical effects
Contents |
Overview
Transthyretin (TTR) is a homotetrameric plasma protein that, as a result, of a set of not yet fully characterized conformational changes, forms, fibrillar aggregates that are the major protein component of amyloid, deposits. More than 80 mutations associated with TTR amyloid deposition, have been described in the literature. X-ray crystallography was used to, elucidate the three-dimensional structure of two important TTR variants:, TTR Y78F, an amyloidogenic protein, and TTR R104H, which is associated, with a protective effect over the amyloidogenic V30M mutation. The, structures of those two TTR variants have been determined in space group, P2(1)2(1)2 to 1.55 and 1.60 angstroms resolution, respectively, using, molecular-replacement techniques. Detailed analysis of the protein model, for TTR Y78F indicates a destabilization of the contacts between the, alpha-helix and AB loop and the body of the molecule, intimately related, to the amyloidogenic nature; contrastingly, in the TTR R104H variant new, contacts involving the N-terminal region and His104 are clearly, antagonists of amyloid formation.
Disease
Known diseases associated with this structure: Amyloid neuropathy, familial, several allelic types OMIM:[176300], Amyloidosis, senile systemic OMIM:[176300], Carpal tunnel syndrome, familial OMIM:[176300], Dystransthyretinemic hyperthyroxinemia OMIM:[176300]
About this Structure
1X7T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
X-ray crystallographic studies of two transthyretin variants: further insights into amyloidogenesis., Neto-Silva RM, Macedo-Ribeiro S, Pereira PJ, Coll M, Saraiva MJ, Damas AM, Acta Crystallogr D Biol Crystallogr. 2005 Mar;61(Pt 3):333-9. Epub 2005, Feb 24. PMID:15735344
Page seeded by OCA on Mon Nov 12 20:01:57 2007
