5ttr
From Proteopedia
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LEU 55 PRO TRANSTHYRETIN CRYSTAL STRUCTURE
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Overview
The x-ray crystal structure of the amyloidogenic Leu55 --> Pro, transthyretin (TTR) variant, implicated as the causative agent in, early-onset familial amyloidotic polyneuropathy (Jacobson, D. R., McFarlin, D. E., Kane, I., and Buxbaum, J. N. (1992) Hum. Genet. 89, 353-356), has been solved by molecular replacement, refined at 2.7 A to a, Rcryst value of 0.190 (Fobs > 2.0sigma), and compared with wild-type, transthyretin to understand the molecular mechanism(s) involved in, amyloidogenesis. Leu55 --> Pro TTR crystallizes in space group C2, with, eight monomers in the asymmetric unit, and the observed packing contacts, are considerably different from those described for the wild-type protein., Refinement of the crystal structure shows that the proline for leucine, substitution disrupts the hydrogen bonds between strands D and A, resulting in different interface contacts. Based on the assumption that, the observed packing contacts may be significant for amyloidogenesis, a, model for the TTR amyloid is proposed. It consists of a tubular structure, with inner and outer diameters approximately of 30 and 100 A and four, monomers per cross-section.
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
5TTR is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of amyloidogenic Leu55 --> Pro transthyretin variant reveals a possible pathway for transthyretin polymerization into amyloid fibrils., Sebastiao MP, Saraiva MJ, Damas AM, J Biol Chem. 1998 Sep 18;273(38):24715-22. PMID:9733771
Page seeded by OCA on Mon Nov 12 23:52:24 2007
