6NR9

hTRiC-hPFD Class5

Summary for 6NR9

• Entry DOI: 10.2210/pdb6nr9/pdb
• EMDB information: 0490 0491 0492 0493 0494 0495 0496
• Descriptor: T-complex protein 1 subunit alpha, Prefoldin subunit 2, Prefoldin subunit 3, ... (14 entities in total)
• Functional Keywords: tric/cct, pfd, cryoem, molecular chaperone, protein folding, chaperone
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 22
• Total formula weight: 981455.53

Authors

Gestaut, D.,Roh, S.H.,Ma, B.,Pintilie, G.,Joachimiak, L.A.,Leitner, A.,Walzthoeni, T.,Aebersold, R.,Chiu, W.,Frydman, J. (deposition date: 2019-01-23, release date: 2019-06-19, Last modification date: 2024-03-20)

Primary citation

Gestaut, D.,Roh, S.H.,Ma, B.,Pintilie, G.,Joachimiak, L.A.,Leitner, A.,Walzthoeni, T.,Aebersold, R.,Chiu, W.,Frydman, J.
The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis.
Cell, 177:751-765.e15, 2019

PubMed Abstract: 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-mass-spectrometry 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.

PubMed: 30955883
DOI: 10.1016/j.cell.2019.03.012

Experimental method

ELECTRON MICROSCOPY (8.5 Å)