5XP1

Structure of monomeric mutant of REI immunoglobulin light chain variable domain crystallized at pH 6

「5B3C」から置き換えられました

5XP1 の概要

• エントリーDOI: 10.2210/pdb5xp1/pdb
• 分子名称: Immunoglobulin kappa variable 1D-33 (2 entities in total)
• 機能のキーワード: immunoglobulin, immune system
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted : P01593
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 95570.13

構造登録者

Mine, S.,Nakamura, T.,Uegaki, K.,Hamada, D. (登録日: 2017-05-31, 公開日: 2017-08-02, 最終更新日: 2025-03-12)

主引用文献

Nawata, M.,Tsutsumi, H.,Kobayashi, Y.,Unzai, S.,Mine, S.,Nakamura, T.,Uegaki, K.,Kamikubo, H.,Kataoka, M.,Hamada, D.
Heat-induced native dimerization prevents amyloid formation by variable domain from immunoglobulin light-chain REI
FEBS J., 284:3114-3127, 2017

PubMed Abstract: Amyloid light-chain (AL) amyloidosis is a protein-misfolding disease characterized by accumulation of immunoglobulin light chains (LCs) into amyloid fibrils. Dimerization of a full length or variable domain (V ) of LC serves to stabilize the native state and prevent the formation of amyloid fibrils. We here analyzed the thermodynamic properties of dimerization and unfolding reactions by nonamyloidogenic V from REI LC or its monomeric Y96K mutant using sedimentation velocity and circular dichroism. The data indicate that the equilibrium shifts to native dimerization for wild-type REI V by elevating temperature due to the negative enthalpy change for dimer dissociation (-81.2 kJ·mol ). The Y96K mutation did not affect the stability of the monomeric native state but increased amyloidogenicity. These results suggest that the heat-induced native homodimerization is the major factor preventing amyloid formation by wild-type REI V . Heat-induced native oligomerization may be an efficient strategy to avoid the formation of misfolded aggregates particularly for thermostable proteins that are used at elevated temperatures under conditions where other proteins tend to misfold.

PubMed: 28736891
DOI: 10.1111/febs.14181

実験手法

X-RAY DIFFRACTION (2.88 Å)