The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.

β/γ-Crystallins, the major structural proteins in human lens, are highly conserved in their tertiary structures but distinct in the quaternary structures. The N- and C-terminal extensions have been proposed to play a crucial role in mediating the size of β-crystallin assembly. In this research, we i...

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Autores principales:	Jia Xu, Sha Wang, Wei-Jie Zhao, Yi-Bo Xi, Yong-Bin Yan, Ke Yao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13c44da62cae46df863722a7f3954052
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spelling	oai:doaj.org-article:13c44da62cae46df863722a7f39540522021-11-18T08:06:08ZThe congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.1932-620310.1371/journal.pone.0051200https://doaj.org/article/13c44da62cae46df863722a7f39540522012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23236454/?tool=EBIhttps://doaj.org/toc/1932-6203β/γ-Crystallins, the major structural proteins in human lens, are highly conserved in their tertiary structures but distinct in the quaternary structures. The N- and C-terminal extensions have been proposed to play a crucial role in mediating the size of β-crystallin assembly. In this research, we investigated the molecular mechanism underlying the congenital hereditary cataract caused by the recently characterized A2V mutation in βB2-crystallin. Spectroscopic experiments indicated that the mutation did not affect the secondary and tertiary structures of βB2-crystallin. The mutation did not affect the formation of βB2/βA3-crystallin heteromer as well as the stability and folding of the heteromer, suggesting that the mutation might not interfere with the protein interacting network in the lens. However, the tetramerization of βB2-crystallin at high protein concentrations was retarded by the A2V mutation. The mutation slightly decreased the thermal stability and promoted the thermal aggregation of βB2-crystallin. Although it did not influence the stability of βB2-crystallin against denaturation induced by chemical denaturants and UV irradiation, the A2V mutant was more prone to be trapped in the off-pathway aggregation process during kinetic refolding. Our results suggested that the A2V mutation might lead to injury of lens optical properties by decreasing βB2-crystallin stability against heat treatment and by impairing βB2-crystallin assembly into high-order homo-oligomers.Jia XuSha WangWei-Jie ZhaoYi-Bo XiYong-Bin YanKe YaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51200 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jia Xu Sha Wang Wei-Jie Zhao Yi-Bo Xi Yong-Bin Yan Ke Yao The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.
description	β/γ-Crystallins, the major structural proteins in human lens, are highly conserved in their tertiary structures but distinct in the quaternary structures. The N- and C-terminal extensions have been proposed to play a crucial role in mediating the size of β-crystallin assembly. In this research, we investigated the molecular mechanism underlying the congenital hereditary cataract caused by the recently characterized A2V mutation in βB2-crystallin. Spectroscopic experiments indicated that the mutation did not affect the secondary and tertiary structures of βB2-crystallin. The mutation did not affect the formation of βB2/βA3-crystallin heteromer as well as the stability and folding of the heteromer, suggesting that the mutation might not interfere with the protein interacting network in the lens. However, the tetramerization of βB2-crystallin at high protein concentrations was retarded by the A2V mutation. The mutation slightly decreased the thermal stability and promoted the thermal aggregation of βB2-crystallin. Although it did not influence the stability of βB2-crystallin against denaturation induced by chemical denaturants and UV irradiation, the A2V mutant was more prone to be trapped in the off-pathway aggregation process during kinetic refolding. Our results suggested that the A2V mutation might lead to injury of lens optical properties by decreasing βB2-crystallin stability against heat treatment and by impairing βB2-crystallin assembly into high-order homo-oligomers.
format	article
author	Jia Xu Sha Wang Wei-Jie Zhao Yi-Bo Xi Yong-Bin Yan Ke Yao
author_facet	Jia Xu Sha Wang Wei-Jie Zhao Yi-Bo Xi Yong-Bin Yan Ke Yao
author_sort	Jia Xu
title	The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.
title_short	The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.
title_full	The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.
title_fullStr	The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.
title_full_unstemmed	The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.
title_sort	congenital cataract-linked a2v mutation impairs tetramer formation and promotes aggregation of βb2-crystallin.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/13c44da62cae46df863722a7f3954052
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The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of βB2-crystallin.

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