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Gestaut, D.* ; Roh, S.H.* ; Ma, B.* ; Pintilie, G.* ; Joachimiak, L.A.* ; Leitner, A.* ; Walzthoeni, T. ; Aebersold, R.* ; Chiu, H.* ; Frydman, J.*

The chaperonin TRiC/CCT associates with prefoldin through a conserved electrostatic interface essential for cellular proteostasis.

Cell 177, 751-765.e15 (2019)
Verlagsversion Preprint Forschungsdaten DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Zeitschrift Cell
Quellenangaben Band: 177, Heft: 3, Seiten: 751-765.e15 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed