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The chaperonin TRiC/CCT associates with prefoldin through a conserved electrostatic interface essential for cellular proteostasis.
Cell 177, 751-765.e15 (2019)
Publ. Version/Full Text
Preprint
Research data
DOI
PMC
Maintaining proteostasis in eukaryotic protein folding involves cooperation of distinct chaperone systems. To understand how the essential ring-shaped chaperonin TRiC/CCT cooperates with the chaperone prefoldin/GIMc (PFD), we integrate cryoelectron microscopy (cryo-EM), crosslinking-masss-pectrometry and biochemical and cellular approaches to elucidate the structural and functional interplay between TRiC/CCT and PFD. We find these hetero-oligomeric chaperones associate in a defined architecture, through a conserved interface of electrostatic contacts that serves as a pivot point for a TRiC-PFD conformational cycle. PFD alternates between an open "latched" conformation and a closed "engaged" conformation that aligns the PFD-TRiC substrate binding chambers. PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles. Disrupting the TRiC-PFD interaction in vivo is strongly deleterious, leading to accumulation of amyloid aggregates. The supra-chaperone assembly formed by PFD and TRiC is essential to prevent toxic conformations and ensure effective cellular proteostasis.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cct ; Chaperone ; Chaperonin ; Cryo-em ; Gimc ; Prefoldin ; Proteostasis ; Tric ; Xl-ms; In-vivo; Proteins; Resolution; Complexes; Binding; Actin; Purification; Aggregation; Polypeptide; Refinement
ISSN (print) / ISBN
0092-8674
e-ISSN
1097-4172
Journal
Cell
Quellenangaben
Volume: 177,
Issue: 3,
Pages: 751-765.e15
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)