3SSG

Structure of transthyretin L55P in complex with Zn

3SSG の概要

• エントリーDOI: 10.2210/pdb3ssg/pdb
• 分子名称: Transthyretin, ZINC ION, CACODYLATE ION, ... (4 entities in total)
• 機能のキーワード: amyloid, transthyretin, hormone
• 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: 1
• 化学式量合計: 14029.12

構造登録者

Castro-Rodrigues, A.F.,Gales, L.,Damas, A.M. (登録日: 2011-07-08, 公開日: 2011-11-30, 最終更新日: 2024-02-28)

主引用文献

Castro-Rodrigues, A.F.,Gales, L.,Saraiva, M.J.,Damas, A.M.
Structural insights into a zinc-dependent pathway leading to Leu55Pro transthyretin amyloid fibrils.
Acta Crystallogr.,Sect.D, 67:1035-1044, 2011

PubMed Abstract: Human transthyretin (TTR) is a homotetrameric protein that is responsible for the formation of amyloid in patients with familiar amyloidotic polyneuropathy (FAP), familiar amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA). Amyloid fibrils are characterized by a cross-β structure. However, details of how TTR monomers are organized to form such an assembly remain unknown. The effect of Zn(2+) in increasing TTR L55P amyloidogenecity has been reported. Crystals of the TTR L55P-Zn(2+) complex were grown under conditions similar to those leading to higher amyloidogenic potential of the variant protein and the three-dimensional structure of the complex was determined by X-ray crystallography. Two different tetrahedral Zn(2+)-binding sites were identified: one cross-links two tetramers, while the other lies at the interface between two monomers in a dimer. The association of monomers involving the two Zn(2+)-binding sites leads to a bidimensional array with a cross-β structure. The formation of this structure and subsequent organization into amyloid fibrils was monitored by fluorescence spectroscopy and electron microscopy. The TTR L55P-Zn(2+) structure offers the first molecular insights into the role of Zn(2+) as a mediator of cross-β-type structure in TTR amyloidosis and the relevance of a Zn(2+)-dependent pathway leading to the production of early amyloidogenic intermediates is discussed.

PubMed: 22120741
DOI: 10.1107/S090744491104491X

実験手法

X-RAY DIFFRACTION (2 Å)