8G7K

mtHsp60 V72I apo focus

8G7K の概要

• エントリーDOI: 10.2210/pdb8g7k/pdb
• 関連するPDBエントリー: 8G7J 8G7L 8G7M 8G7N 8G7O
• EMDBエントリー: 29813 29814 29815 29816 29817 29818
• 分子名称: 60 kDa heat shock protein, mitochondrial (1 entity in total)
• 機能のキーワード: chaperonin, atpase, foldase, chaperone
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 408247.00

構造登録者

Braxton, J.R.,Shao, H.,Tse, E.,Gestwicki, J.E.,Southworth, D.R. (登録日: 2023-02-16, 公開日: 2023-07-12, 最終更新日: 2024-06-19)

主引用文献

Braxton, J.R.,Shao, H.,Tse, E.,Gestwicki, J.E.,Southworth, D.R.
Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly.
Biorxiv, 2023

PubMed Abstract: The mitochondrial chaperonin, mtHsp60, promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin binds to clients and progresses through its ATP-dependent reaction cycle are not clear. Here, we determined cryo-electron microscopy (cryo-EM) structures of a hyperstable disease-associated mtHsp60 mutant, V72I, at three stages in this cycle. Unexpectedly, client density is identified in all states, revealing interactions with mtHsp60's apical domains and C-termini that coordinate client positioning in the folding chamber. We further identify a striking asymmetric arrangement of the apical domains in the ATP state, in which an alternating up/down configuration positions interaction surfaces for simultaneous recruitment of mtHsp10 and client retention. Client is then fully encapsulated in mtHsp60/mtHsp10, revealing prominent contacts at two discrete sites that potentially support maturation. These results identify a new role for the apical domains in coordinating client capture and progression through the cycle, and suggest a conserved mechanism of group I chaperonin function.

PubMed: 37293102
DOI: 10.1101/2023.05.15.540872

実験手法

ELECTRON MICROSCOPY (3.8 Å)