3DVI

Crystal structure of kappa 1 amyloidogenic light chain variable domain

3DVI の概要

• エントリーDOI: 10.2210/pdb3dvi/pdb
• 関連するPDBエントリー: 2q1e 2q20
• 分子名称: Amyloidogenic light chain variable domain AL-103 (2 entities in total)
• 機能のキーワード: al, light chain amyloidosis, amyloid, immunoglobulin, light chain, light chain variable domain, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11972.26

構造登録者

Thompson, J.R.,Randles, E.G.,Ramirez-Alvarado, M. (登録日: 2008-07-18, 公開日: 2009-05-12, 最終更新日: 2024-11-20)

主引用文献

Randles, E.G.,Thompson, J.R.,Martin, D.J.,Ramirez-Alvarado, M.
Structural alterations within native amyloidogenic immunoglobulin light chains.
J.Mol.Biol., 389:199-210, 2009

PubMed Abstract: Amyloid diseases are characterized by the misfolding of a precursor protein that leads to amyloid fibril formation. Despite the fact that there are different precursors, some commonalities in the misfolding mechanism are thought to exist. In light chain amyloidosis (AL), the immunoglobulin light chain forms amyloid fibrils that deposit in the extracellular space of vital organs. AL proteins are thermodynamically destabilized compared to non-amyloidogenic proteins and some studies have linked this instability to increased fibril formation rates. Here we present the crystal structures of two highly homologous AL proteins, AL-12 and AL-103. This structural study shows that these proteins retain the canonical germ line dimer interface. We highlight important structural alterations in two loops flanking the dimer interface and correlate these results with the somatic mutations present in AL-12 and AL-103. We suggest that these alterations are informative structural features that are likely contributing to protein instability that leads to conformational changes involved in the initial events of amyloid formation.

PubMed: 19361523
DOI: 10.1016/j.jmb.2009.04.010

実験手法

X-RAY DIFFRACTION (1.53 Å)