3CDC

kI O18/O8 N34I/Y87H immunoglobulin light chain variable domain

3CDC の概要

• エントリーDOI: 10.2210/pdb3cdc/pdb
• 関連するPDBエントリー: 3CDF 3CDY
• 分子名称: Light Chain Amyloidogenic (2 entities in total)
• 機能のキーワード: greek key beta barrel, amyloid, immunoglobulin, light chain, variable domain, immune system
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23890.29

構造登録者

Baden, E.M.,Randles, E.G.,Thompson, J.R.,Ramirez-Alvarado, M. (登録日: 2008-02-26, 公開日: 2008-09-02, 最終更新日: 2024-10-30)

主引用文献

Baden, E.M.,Randles, E.G.,Aboagye, A.K.,Thompson, J.R.,Ramirez-Alvarado, M.
Structural insights into the role of mutations in amyloidogenesis.
J.Biol.Chem., 283:30950-30956, 2008

PubMed Abstract: Mechanisms of amyloidogenesis are not well understood, including potential structural contributions of mutations in the process. Our previous research indicated that the dimer interface of amyloidogenic immunoglobulin light chain protein AL-09 is twisted 90 degrees relative to the protein from its germline sequence, kappaI O18/O8. Here we report a systematic restoration of AL-09 to its germline sequence by mutating the non-conservative somatic mutations located in the light chain dimer interface. Among these mutants, we find a correlation between increased thermodynamic stability and an increase in the lag time for fibril formation. The restorative mutant AL-09 H87Y completes the trifecta and restores the dimer interface observed in kappaI O18/O8, emphasizing the potential importance of the structural integrity of these proteins to protect against amyloidogenicity. We also find that adding amyloidogenic mutations into the germline protein illustrates mutational cooperativity in promoting amyloidogenesis.

PubMed: 18768467
DOI: 10.1074/jbc.M804822200

実験手法

X-RAY DIFFRACTION (1.53 Å)