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The ATP-powered gymnastics of TRiC/CCT: an asymmetric protein folding machine with a symmetric origin story.

ABSTRACT: The eukaryotic chaperonin TRiC/CCT is a large hetero-oligomeric complex that plays an essential role assisting cellular protein folding and suppressing protein aggregation. It consists of two rings, and each composed of eight different subunits; non-native polypeptides bind and fold in an ATP-dependent manner within their central chamber. Here, we review recent advances in our understanding of TRiC structure and mechanism enabled by application of hybrid structural methods including the integration of cryo-electron microscopy with distance constraints from crosslinking mass spectrometry. These new insights are revealing how the different TRiC/CCT subunits create asymmetry in its ATP-driven conformational cycle and its interaction with non-native polypeptides, which ultimately underlie its unique ability to fold proteins that cannot be folded by other chaperones.

SUBMITTER: Gestaut D

PROVIDER: S-EPMC6776438 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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The ATP-powered gymnastics of TRiC/CCT: an asymmetric protein folding machine with a symmetric origin story.

Gestaut Daniel D Limatola Antonio A Joachimiak Lukasz L Frydman Judith J

Current opinion in structural biology 20190409

The eukaryotic chaperonin TRiC/CCT is a large hetero-oligomeric complex that plays an essential role assisting cellular protein folding and suppressing protein aggregation. It consists of two rings, and each composed of eight different subunits; non-native polypeptides bind and fold in an ATP-dependent manner within their central chamber. Here, we review recent advances in our understanding of TRiC structure and mechanism enabled by application of hybrid structural methods including the integrat ...[more]

PMID: 30978594

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A gradient of ATP affinities generates an asymmetric power stroke driving the chaperonin TRIC/CCT folding cycle.

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