1fh2

From Proteopedia

---

Revision as of 14:46, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1fh2, resolution 1.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

TRANSTHYRETIN STABILITY AS A KEY FACTOR IN AMYLOIDOGENESIS

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Transthyretin (TTR) amyloidosis is a conformational disturbance, which, like other amyloidoses, represents a life threat. Here, we report a TTR, variant, TTR Thr119Met, that has been shown to have a protective role in, the development of clinical symptoms in carriers of TTR Val30Met, one of, the most frequent variants among TTR amyloidosis patients. In order to, understand this effect, we have determined the structures of the TTR, Val30Met/Thr119Met double mutant isolated from the serum of one patient, and of both the native and thyroxine complex of TTR Thr119Met. Major, conclusions are: (i) new H-bonds within each monomer and monomer-monomer, inter-subunit contacts, e.g. Ser117-Ser117 and Met119-Tyr114, increase, protein stability, possibly leading to the protective effect of the TTR, Val30Met/Thr119Met variant when compared to the single variant TTR, Val30Met. (ii) The mutated residue (Met119) extends across the thyroxine, binding channel inducing conformational changes that lead to closer, contacts between different dimers within the tetramer. The data, at atomic, resolution, were essential to detect, for the first time, the subtle, changes in the inter-subunit contacts of TTR, and explain the, non-amyloidogenic potential of the TTR Thr119Met variant, improving, considerably current research on the TTR amyloid fibril formation pathway.

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

1FH2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at atomic resolution., Sebastiao MP, Lamzin V, Saraiva MJ, Damas AM, J Mol Biol. 2001 Mar 2;306(4):733-44. PMID:11243784

Page seeded by OCA on Mon Nov 12 16:53:12 2007