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Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT

The cytoskeletal proteins tubulin and actin are the obligate substrates of TCP-1 ring complex/Chaperonin containing TCP-1 (TRiC/CCT), and their folding involves co-chaperone. Through cryo–electron microscopy analysis, we present a more complete picture of TRiC-assisted tubulin/actin folding along TR...

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Autores principales: Han, Wenyu, Jin, Mingliang, Liu, Caixuan, Zhao, Qiaoyu, Wang, Shutian, Wang, Yifan, Yin, Yue, Peng, Chao, Wang, Yanxing, Cong, Yao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017041/
https://www.ncbi.nlm.nih.gov/pubmed/36921056
http://dx.doi.org/10.1126/sciadv.ade1207
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author Han, Wenyu
Jin, Mingliang
Liu, Caixuan
Zhao, Qiaoyu
Wang, Shutian
Wang, Yifan
Yin, Yue
Peng, Chao
Wang, Yanxing
Cong, Yao
author_facet Han, Wenyu
Jin, Mingliang
Liu, Caixuan
Zhao, Qiaoyu
Wang, Shutian
Wang, Yifan
Yin, Yue
Peng, Chao
Wang, Yanxing
Cong, Yao
author_sort Han, Wenyu
collection PubMed
description The cytoskeletal proteins tubulin and actin are the obligate substrates of TCP-1 ring complex/Chaperonin containing TCP-1 (TRiC/CCT), and their folding involves co-chaperone. Through cryo–electron microscopy analysis, we present a more complete picture of TRiC-assisted tubulin/actin folding along TRiC adenosine triphosphatase cycle, under the coordination of co-chaperone plp2. In the open S1/S2 states, plp2 and tubulin/actin engaged within opposite TRiC chambers. Notably, we captured an unprecedented TRiC-plp2-tubulin complex in the closed S3 state, engaged with a folded full-length β-tubulin and loaded with a guanosine triphosphate, and a plp2 occupying opposite rings. Another closed S4 state revealed an actin in the intermediate folding state and a plp2. Accompanying TRiC ring closure, plp2 translocation could coordinate substrate translocation on the CCT6 hemisphere, facilitating substrate stabilization and folding. Our findings reveal the folding mechanism of the major cytoskeletal proteins tubulin/actin under the coordination of the biogenesis machinery TRiC and plp2 and extend our understanding of the links between cytoskeletal proteostasis and related human diseases.
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spelling pubmed-100170412023-03-16 Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT Han, Wenyu Jin, Mingliang Liu, Caixuan Zhao, Qiaoyu Wang, Shutian Wang, Yifan Yin, Yue Peng, Chao Wang, Yanxing Cong, Yao Sci Adv Biomedicine and Life Sciences The cytoskeletal proteins tubulin and actin are the obligate substrates of TCP-1 ring complex/Chaperonin containing TCP-1 (TRiC/CCT), and their folding involves co-chaperone. Through cryo–electron microscopy analysis, we present a more complete picture of TRiC-assisted tubulin/actin folding along TRiC adenosine triphosphatase cycle, under the coordination of co-chaperone plp2. In the open S1/S2 states, plp2 and tubulin/actin engaged within opposite TRiC chambers. Notably, we captured an unprecedented TRiC-plp2-tubulin complex in the closed S3 state, engaged with a folded full-length β-tubulin and loaded with a guanosine triphosphate, and a plp2 occupying opposite rings. Another closed S4 state revealed an actin in the intermediate folding state and a plp2. Accompanying TRiC ring closure, plp2 translocation could coordinate substrate translocation on the CCT6 hemisphere, facilitating substrate stabilization and folding. Our findings reveal the folding mechanism of the major cytoskeletal proteins tubulin/actin under the coordination of the biogenesis machinery TRiC and plp2 and extend our understanding of the links between cytoskeletal proteostasis and related human diseases. American Association for the Advancement of Science 2023-03-15 /pmc/articles/PMC10017041/ /pubmed/36921056 http://dx.doi.org/10.1126/sciadv.ade1207 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Han, Wenyu
Jin, Mingliang
Liu, Caixuan
Zhao, Qiaoyu
Wang, Shutian
Wang, Yifan
Yin, Yue
Peng, Chao
Wang, Yanxing
Cong, Yao
Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT
title Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT
title_full Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT
title_fullStr Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT
title_full_unstemmed Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT
title_short Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT
title_sort structural basis of plp2-mediated cytoskeletal protein folding by tric/cct
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017041/
https://www.ncbi.nlm.nih.gov/pubmed/36921056
http://dx.doi.org/10.1126/sciadv.ade1207
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