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Conformational folding and disulfide bonding drive distinct stages of protein structure formation

The causal relationship between conformational folding and disulfide bonding in protein oxidative folding remains incompletely defined. Here we show a stage-dependent interplay between the two events in oxidative folding of C-reactive protein (CRP) in live cells. CRP is composed of five identical su...

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Autores principales: Lv, Jian-Min, Lü, Shou-Qin, Liu, Zu-Pei, Zhang, Juan, Gao, Bo-Xuan, Yao, Zhen-Yu, Wu, Yue-Xin, Potempa, Lawrence A., Ji, Shang-Rong, Long, Mian, Wu, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784126/
https://www.ncbi.nlm.nih.gov/pubmed/29367639
http://dx.doi.org/10.1038/s41598-018-20014-y
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author Lv, Jian-Min
Lü, Shou-Qin
Liu, Zu-Pei
Zhang, Juan
Gao, Bo-Xuan
Yao, Zhen-Yu
Wu, Yue-Xin
Potempa, Lawrence A.
Ji, Shang-Rong
Long, Mian
Wu, Yi
author_facet Lv, Jian-Min
Lü, Shou-Qin
Liu, Zu-Pei
Zhang, Juan
Gao, Bo-Xuan
Yao, Zhen-Yu
Wu, Yue-Xin
Potempa, Lawrence A.
Ji, Shang-Rong
Long, Mian
Wu, Yi
author_sort Lv, Jian-Min
collection PubMed
description The causal relationship between conformational folding and disulfide bonding in protein oxidative folding remains incompletely defined. Here we show a stage-dependent interplay between the two events in oxidative folding of C-reactive protein (CRP) in live cells. CRP is composed of five identical subunits, which first fold spontaneously to a near-native core with a correctly positioned C-terminal helix. This process drives the formation of the intra-subunit disulfide bond between Cys36 and Cys97. The second stage of subunit folding, however, is a non-spontaneous process with extensive restructuring driven instead by the intra-subunit disulfide bond and guided by calcium binding-mediated anchoring. With the folded subunits, pentamer assembly ensues. Our results argue that folding spontaneity is the major determinant that dictates which event acts as the driver. The stepwise folding pathway of CRP further suggests that one major route might be selected out of the many in theory for efficient folding in the cellular environment.
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spelling pubmed-57841262018-02-07 Conformational folding and disulfide bonding drive distinct stages of protein structure formation Lv, Jian-Min Lü, Shou-Qin Liu, Zu-Pei Zhang, Juan Gao, Bo-Xuan Yao, Zhen-Yu Wu, Yue-Xin Potempa, Lawrence A. Ji, Shang-Rong Long, Mian Wu, Yi Sci Rep Article The causal relationship between conformational folding and disulfide bonding in protein oxidative folding remains incompletely defined. Here we show a stage-dependent interplay between the two events in oxidative folding of C-reactive protein (CRP) in live cells. CRP is composed of five identical subunits, which first fold spontaneously to a near-native core with a correctly positioned C-terminal helix. This process drives the formation of the intra-subunit disulfide bond between Cys36 and Cys97. The second stage of subunit folding, however, is a non-spontaneous process with extensive restructuring driven instead by the intra-subunit disulfide bond and guided by calcium binding-mediated anchoring. With the folded subunits, pentamer assembly ensues. Our results argue that folding spontaneity is the major determinant that dictates which event acts as the driver. The stepwise folding pathway of CRP further suggests that one major route might be selected out of the many in theory for efficient folding in the cellular environment. Nature Publishing Group UK 2018-01-24 /pmc/articles/PMC5784126/ /pubmed/29367639 http://dx.doi.org/10.1038/s41598-018-20014-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lv, Jian-Min
Lü, Shou-Qin
Liu, Zu-Pei
Zhang, Juan
Gao, Bo-Xuan
Yao, Zhen-Yu
Wu, Yue-Xin
Potempa, Lawrence A.
Ji, Shang-Rong
Long, Mian
Wu, Yi
Conformational folding and disulfide bonding drive distinct stages of protein structure formation
title Conformational folding and disulfide bonding drive distinct stages of protein structure formation
title_full Conformational folding and disulfide bonding drive distinct stages of protein structure formation
title_fullStr Conformational folding and disulfide bonding drive distinct stages of protein structure formation
title_full_unstemmed Conformational folding and disulfide bonding drive distinct stages of protein structure formation
title_short Conformational folding and disulfide bonding drive distinct stages of protein structure formation
title_sort conformational folding and disulfide bonding drive distinct stages of protein structure formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784126/
https://www.ncbi.nlm.nih.gov/pubmed/29367639
http://dx.doi.org/10.1038/s41598-018-20014-y
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