TY - JOUR
T1 - The ATP-powered gymnastics of TRiC/CCT
T2 - an asymmetric protein folding machine with a symmetric origin story
AU - Gestaut, Daniel
AU - Limatola, Antonio
AU - Joachimiak, Lukasz
AU - Frydman, Judith
N1 - Funding Information:
Work in the Frydman lab is supported by N.I.H. ( R01GM074074 to JF; F32GM103124 to DG). We thank members of the Frydman lab for discussions.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.sbi.2019.03.002
DO - 10.1016/j.sbi.2019.03.002
M3 - Review article
C2 - 30978594
AN - SCOPUS:85063985520
SN - 0959-440X
VL - 55
SP - 50
EP - 58
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
ER -