6SM1

Wild type immunoglobulin light chain (WT-1)

6SM1 の概要

• エントリーDOI: 10.2210/pdb6sm1/pdb
• 関連するPDBエントリー: 4nki
• 分子名称: Immunoglobulin lambda variable 2-14, CALCIUM ION, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• 機能のキーワード: al amyloidosis, antibody folding, protein stability, dynamics, immune system
• 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: 12371.54

構造登録者

Kazman, P.,Vielberg, M.-T.,Cendales, M.D.P.,Hunziger, L.,Weber, B.,Hegenbart, U.,Zacharias, M.,Koehler, R.,Schoenland, S.,Groll, M.,Buchner, J. (登録日: 2019-08-21, 公開日: 2020-03-18, 最終更新日: 2024-11-13)

主引用文献

Kazman, P.,Vielberg, M.T.,Pulido Cendales, M.D.,Hunziger, L.,Weber, B.,Hegenbart, U.,Zacharias, M.,Kohler, R.,Schonland, S.,Groll, M.,Buchner, J.
Fatal amyloid formation in a patient's antibody light chain is caused by a single point mutation.
Elife, 9:-, 2020

PubMed Abstract: In systemic light chain amyloidosis, an overexpressed antibody light chain (LC) forms fibrils which deposit in organs and cause their failure. While it is well-established that mutations in the LC's V domain are important prerequisites, the mechanisms which render a patient LC amyloidogenic are ill-defined. In this study, we performed an in-depth analysis of the factors and mutations responsible for the pathogenic transformation of a patient-derived λ LC, by recombinantly expressing variants in . We show that proteolytic cleavage of the patient LC resulting in an isolated V domain is essential for fibril formation. Out of 11 mutations in the patient V, only one, a leucine to valine mutation, is responsible for fibril formation. It disrupts a hydrophobic network rendering the C-terminal segment of V more dynamic and decreasing domain stability. Thus, the combination of proteolytic cleavage and the destabilizing mutation trigger conformational changes that turn the LC pathogenic.

PubMed: 32151314
DOI: 10.7554/eLife.52300

実験手法

X-RAY DIFFRACTION (1.55 Å)