The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.

γD-crystallin is one of the major structural proteins in human eye lens. The solubility and stability of γD-crystallin play a crucial role in maintaining the optical properties of the lens during the life span of an individual. Previous study has shown that the inherited mutation G61C results in aut...

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Autores principales:	Wang Zhang, Hong-Chen Cai, Fei-Feng Li, Yi-Bo Xi, Xu Ma, Yong-Bin Yan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a522b9c2fbc149e1beb58c67e3f38df4
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spelling	oai:doaj.org-article:a522b9c2fbc149e1beb58c67e3f38df42021-11-18T06:52:53ZThe congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.1932-620310.1371/journal.pone.0020564https://doaj.org/article/a522b9c2fbc149e1beb58c67e3f38df42011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21655238/?tool=EBIhttps://doaj.org/toc/1932-6203γD-crystallin is one of the major structural proteins in human eye lens. The solubility and stability of γD-crystallin play a crucial role in maintaining the optical properties of the lens during the life span of an individual. Previous study has shown that the inherited mutation G61C results in autosomal dominant congenital cataract. In this research, we studied the effects of the G61C mutation on γD-crystallin structure, stability and aggregation via biophysical methods. CD, intrinsic and extrinsic fluorescence spectroscopy indicated that the G61C mutation did not affect the native structure of γD-crystallin. The stability of γD-crystallin against heat- or GdnHCl-induced denaturation was significantly decreased by the mutation, while no influence was observed on the acid-induced unfolding. The mutation mainly affected the transition from the native state to the intermediate but not that from the intermediate to the unfolded or aggregated states. At high temperatures, both proteins were able to form aggregates, and the aggregation of the mutant was much more serious than the wild type protein at the same temperature. At body temperature and acidic conditions, the mutant was more prone to form amyloid-like fibrils. The aggregation-prone property of the mutant was not altered by the addition of reductive reagent. These results suggested that the decrease in protein stability followed by aggregation-prone property might be the major cause in the hereditary cataract induced by the G61C mutation.Wang ZhangHong-Chen CaiFei-Feng LiYi-Bo XiXu MaYong-Bin YanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20564 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wang Zhang Hong-Chen Cai Fei-Feng Li Yi-Bo Xi Xu Ma Yong-Bin Yan The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.
description	γD-crystallin is one of the major structural proteins in human eye lens. The solubility and stability of γD-crystallin play a crucial role in maintaining the optical properties of the lens during the life span of an individual. Previous study has shown that the inherited mutation G61C results in autosomal dominant congenital cataract. In this research, we studied the effects of the G61C mutation on γD-crystallin structure, stability and aggregation via biophysical methods. CD, intrinsic and extrinsic fluorescence spectroscopy indicated that the G61C mutation did not affect the native structure of γD-crystallin. The stability of γD-crystallin against heat- or GdnHCl-induced denaturation was significantly decreased by the mutation, while no influence was observed on the acid-induced unfolding. The mutation mainly affected the transition from the native state to the intermediate but not that from the intermediate to the unfolded or aggregated states. At high temperatures, both proteins were able to form aggregates, and the aggregation of the mutant was much more serious than the wild type protein at the same temperature. At body temperature and acidic conditions, the mutant was more prone to form amyloid-like fibrils. The aggregation-prone property of the mutant was not altered by the addition of reductive reagent. These results suggested that the decrease in protein stability followed by aggregation-prone property might be the major cause in the hereditary cataract induced by the G61C mutation.
format	article
author	Wang Zhang Hong-Chen Cai Fei-Feng Li Yi-Bo Xi Xu Ma Yong-Bin Yan
author_facet	Wang Zhang Hong-Chen Cai Fei-Feng Li Yi-Bo Xi Xu Ma Yong-Bin Yan
author_sort	Wang Zhang
title	The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.
title_short	The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.
title_full	The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.
title_fullStr	The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.
title_full_unstemmed	The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.
title_sort	congenital cataract-linked g61c mutation destabilizes γd-crystallin and promotes non-native aggregation.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/a522b9c2fbc149e1beb58c67e3f38df4
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The congenital cataract-linked G61C mutation destabilizes γD-crystallin and promotes non-native aggregation.

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