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-Structure paper
タイトル | The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis. |
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ジャーナル・号・ページ | Cell, Vol. 177, Issue 3, Page 751-765.e15, Year 2019 |
掲載日 | 2019年4月18日 |
著者 | Daniel Gestaut / Soung Hun Roh / Boxue Ma / Grigore Pintilie / Lukasz A Joachimiak / Alexander Leitner / Thomas Walzthoeni / Ruedi Aebersold / Wah Chiu / Judith Frydman / |
PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:30955883 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 6.5 - 8.7 Å |
構造データ | EMDB-0496: |
由来 |
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キーワード | CHAPERONE / TRiC/CCT / PFD / CryoEM / Molecular Chaperone / Protein folding |