5TTR

LEU 55 PRO TRANSTHYRETIN CRYSTAL STRUCTURE

5TTR の概要

• エントリーDOI: 10.2210/pdb5ttr/pdb
• 分子名称: TRANSTHYRETIN (1 entity in total)
• 機能のキーワード: transthyretin, amyloid, fap, thyroxine, transport
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02766
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 110090.54

構造登録者

Sebastiao, M.P.,Saraiva, M.J.,Damas, A.M. (登録日: 1998-04-30, 公開日: 1999-06-01, 最終更新日: 2024-05-22)

主引用文献

Sebastiao, M.P.,Saraiva, M.J.,Damas, A.M.
The crystal structure of amyloidogenic Leu55 --> Pro transthyretin variant reveals a possible pathway for transthyretin polymerization into amyloid fibrils.
J.Biol.Chem., 273:24715-24722, 1998

PubMed Abstract: 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.

PubMed: 9733771
DOI: 10.1074/jbc.273.38.24715

実験手法

X-RAY DIFFRACTION (2.7 Å)