5IR3

Crystal structure of the recombinant highest fibrillogenic natural mutant (obtained from patient AR) derived from lambda 6 light chain variable domain

5IR3 の概要

• エントリーDOI: 10.2210/pdb5ir3/pdb
• 関連するPDBエントリー: 2W0K 3B5G 3BDX 5C9K
• 分子名称: Ig lambda chain V-VI region AR, ACETATE ION (3 entities in total)
• 機能のキーワード: beta-sandwich, immunoglobulin, al amyloidosis, immune system
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted : P01721
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11985.86

構造登録者

Hernandez-Santoyo, A.,Rodriguez-Romero, A. (登録日: 2016-03-11, 公開日: 2017-06-14, 最終更新日: 2024-11-06)

主引用文献

Luna-Martinez, O.D.,Hernandez-Santoyo, A.,Villalba-Velazquez, M.I.,Sanchez-Alcala, R.,Fernandez-Velasco, D.A.,Becerril, B.
Stabilizing an amyloidogenic lambda 6 light chain variable domain.
FEBS J., 284:3702-3717, 2017

PubMed Abstract: Light chain amyloidosis is a lethal disease where vital organs are damaged by the fibrillar aggregation of monoclonal light chains. λ6a is an immunoglobulin light chain encoded by the germ-line gene segment implicated in this disease. AR is a patient-derived germ-line variant with a markedly low thermodynamic stability and prone to form fibrils in vitro in less than an hour. Here, we sought to stabilize this domain by mutating some residues back to the germ-line sequence, and the most stabilizing mutations were the single-mutant AR-F21I and the double-mutant AR-F21/IV104L, both located in the hydrophobic core. While mutation Arg25Gly in 6aJL2 destabilized the domain, mutating Gly25 back to arginine in AR did not contribute to stabilization as expected. Crystallographic structures of AR and 6a-R25G were generated to explain this discrepancy. Finally, 6a-R25G crystals revealed an octameric assembly which was emulated into 6aJL2 and AR crystals by replicating their structural parameters and suggesting a common assembly pattern.

PubMed: 28898537
DOI: 10.1111/febs.14265

実験手法

X-RAY DIFFRACTION (1.7 Å)