9ES0

ATP-bound human mitochondrial Hsp60-Hsp10 football complex

Summary for 9ES0

• Entry DOI: 10.2210/pdb9es0/pdb
• EMDB information: 19930 19931 19932 19933 19934 19936
• Descriptor: 60 kDa heat shock protein, mitochondrial, 10 kDa heat shock protein, mitochondrial, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: mitochondrial, d7-symmetry, chaperone
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 28
• Total formula weight: 975745.43

Authors

Lopez-Alonso, J.P.,Tascon, I.,Ubarretxena-Belandia, I. (deposition date: 2024-03-25, release date: 2025-04-09, Last modification date: 2025-12-10)

Primary citation

Tascon, I.,Lopez-Alonso, J.P.,Shkolnisky, Y.,Gil-Carton, D.,Vilchez-Garcia, J.,Berruezo, A.G.,Gomez-Llorente, Y.,Malik, R.,Jebara, F.,Patra, M.,Hirsch, J.A.,Azem, A.,Ubarretxena-Belandia, I.
Structural basis for ATP-driven double-ring assembly of the human mitochondrial Hsp60 chaperonin.
Biorxiv, 2025

PubMed Abstract: The ATP-driven mHsp60:mHsp10 chaperonin system assists protein folding within the mitochondrial matrix of human cells. Substrate protein folding has been proposed to occur through interconnected single- and double-ring pathways. In the absence of nucleotide, mHsp60 exists in equilibrium between free protomers and heptameric single rings, while the formation of double rings requires ATP. Here, we present cryo-electron microscopy structures of mHsp60 in the apo state, bound to ATP, and bound to ATP in complex with the cochaperonin mHsp10. ATP binding to single-ring apo mHsp60 triggers coordinated conformational changes in the intermediate and apical domains, resulting in a highly dynamic apical region within the ring. Extensive inter-subunit rearrangements flatten the equatorial surface of each ring, thereby enabling inter-ring contacts that stitch the rings together to form double-ring mHsp60 . Collectively, these structures define the structural basis of ATP-driven double-ring assembly of a human mitochondrial chaperonin responsible for maintaining mitochondrial protein homeostasis.

PubMed: 41256524
DOI: 10.1101/2025.10.04.680452

Experimental method

ELECTRON MICROSCOPY (2.58 Å)