2Q1E

Altered dimer interface decreases stability in an amyloidogenic kappa1 Bence Jones protein.

2Q1E の概要

• エントリーDOI: 10.2210/pdb2q1e/pdb
• 分子名称: Amyloidogenic immunoglobulin light chain protein AL-09, SULFATE ION (3 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: 4
• 化学式量合計: 47920.65

構造登録者

Thompson, J.R.,Ramirez-Alvarado, M.,Baden, E.M. (登録日: 2007-05-24, 公開日: 2008-04-08, 最終更新日: 2024-10-30)

主引用文献

Baden, E.M.,Owen, B.A.,Peterson, F.C.,Volkman, B.F.,Ramirez-Alvarado, M.,Thompson, J.R.
Altered dimer interface decreases stability in an amyloidogenic protein.
J.Biol.Chem., 283:15853-15860, 2008

PubMed Abstract: Amyloidoses are devastating and currently incurable diseases in which the process of amyloid formation causes fatal cellular and organ damage. The molecular mechanisms underlying amyloidoses are not well known. In this study, we address the structural basis of immunoglobulin light chain amyloidosis, which results from deposition of light chains produced by clonal plasma cells. We compare light chain amyloidosis protein AL-09 to its wild-type counterpart, the kappaI O18/O8 light chain germline. Crystallographic studies indicate that both proteins form dimers. However, AL-09 has an altered dimer interface that is rotated 90 degrees from the kappaI O18/O8 dimer interface. The three non-conservative mutations in AL-09 are located within the dimer interface, consistent with their role in the decreased stability of this amyloidogenic protein. Moreover, AL-09 forms amyloid fibrils more quickly than kappaI O18/O8 in vitro. These results support the notion that the increased stability of the monomer and delayed fibril formation, together with a properly formed dimer, may be protective against amyloidogenesis. This could open a new direction into rational drug design for amyloidogenic proteins.

PubMed: 18400753
DOI: 10.1074/jbc.M705347200

実験手法

X-RAY DIFFRACTION (2.55 Å)