9BEE

alphaB-crystallin N-terminal IXI variant in a fibril state

9BEE の概要

• エントリーDOI: 10.2210/pdb9bee/pdb
• EMDBエントリー: 44477
• 分子名称: Alpha-crystallin B chain (2 entities in total)
• 機能のキーワード: small heat-shock protein fibril proteostasis cataract, chaperone
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22050.93

構造登録者

McFarland, R.,Reichow, S.L. (登録日: 2024-04-15, 公開日: 2024-12-11)

主引用文献

McFarland, R.,Noroozi, R.,Miller, A.P.,Reichow, S.L.
Dynamic fibrillar assembly of alpha B-crystallin induced by perturbation of the conserved NT-IXI motif resolved by cryo-EM.
Nat Commun, 15:10336-10336, 2024

PubMed Abstract: αB-crystallin is an archetypical member of the small heat shock proteins (sHSPs) vital for cellular proteostasis and mitigating protein misfolding diseases. Gaining insights into the principles defining their molecular organization and chaperone function have been hindered by intrinsic dynamic properties and limited high-resolution structural analysis. To disentangle the mechanistic underpinnings of these dynamical properties, we ablate a conserved IXI-motif located within the N-terminal (NT) domain of human αB-crystallin implicated in subunit exchange dynamics and client sequestration. This results in a profound structural transformation, from highly polydispersed caged-like native assemblies into an elongated fibril state amenable to high-resolution cryo-EM analysis. The reversible nature of this variant facilitates interrogation of functional effects due to perturbation of the NT-IXI motif in both the native-like oligomer and fibril states. Together, our investigations unveil several features thought to be key mechanistic attributes to sHSPs and point to a critical significance of the NT-IXI motif in αB-crystallin assembly, polydispersity, and chaperone activity.

PubMed: 39609421
DOI: 10.1038/s41467-024-54647-7

実験手法

ELECTRON MICROSCOPY (3.4 Å)