8G7L

ATP-bound mtHsp60 V72I

Summary for 8G7L

• Entry DOI: 10.2210/pdb8g7l/pdb
• Related: 8G7J 8G7K 8G7M 8G7N 8G7O
• EMDB information: 29813 29814 29815 29816 29817 29818
• Descriptor: 60 kDa heat shock protein, mitochondrial, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: chaperonin, atpase, foldase, chaperone
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 14
• Total formula weight: 824482.18

Authors

Braxton, J.R.,Shao, H.,Tse, E.,Gestwicki, J.E.,Southworth, D.R. (deposition date: 2023-02-16, release date: 2023-07-12, Last modification date: 2024-06-19)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.5 Å)