6NRC

hTRiC-hPFD Class3

6NRC の概要

• エントリーDOI: 10.2210/pdb6nrc/pdb
• EMDBエントリー: 0490 0491 0492 0493 0494 0495 0496
• 分子名称: Prefoldin subunit 1, T-complex protein 1 subunit delta, T-complex protein 1 subunit epsilon, ... (14 entities in total)
• 機能のキーワード: tric/cct, pfd, cryoem, molecular chaperone, protein folding, chaperone
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 981455.53

構造登録者

Gestaut, D.,Roh, S.H.,Ma, B.,Pintilie, G.,Joachimiak, L.A.,Leitner, A.,Walzthoeni, T.,Aebersold, R.,Chiu, W.,Frydman, J. (登録日: 2019-01-23, 公開日: 2019-06-19, 最終更新日: 2024-03-20)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (8.3 Å)