Heat-induced denaturation of cataract-related human γD-crystallin

Objective To reveal the thermally induced denaturation of wild-type human γD-crystallin(HGD) and congenital cataract-related mutant (HGD P23T), and compare the differences in the structural changes between wild-type and mutants during a heating process. Methods HGD and HGD P23T were expressed and...

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Main Author: ZHOU Xin, LI Zhenyan, LI Shuyuan, ZHANG Wenbo, WANG Chenxuan
Format: Article
Language:zho
Published: Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. 2025-01-01
Series:Jichu yixue yu linchuang
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Online Access:https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-1-1.pdf
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author ZHOU Xin, LI Zhenyan, LI Shuyuan, ZHANG Wenbo, WANG Chenxuan
author_facet ZHOU Xin, LI Zhenyan, LI Shuyuan, ZHANG Wenbo, WANG Chenxuan
author_sort ZHOU Xin, LI Zhenyan, LI Shuyuan, ZHANG Wenbo, WANG Chenxuan
collection DOAJ
description Objective To reveal the thermally induced denaturation of wild-type human γD-crystallin(HGD) and congenital cataract-related mutant (HGD P23T), and compare the differences in the structural changes between wild-type and mutants during a heating process. Methods HGD and HGD P23T were expressed and purified. The temperature-dependent intrinsic fluorescence intensity and static light scattering intensity of the protein samples were measured to reveal the temperature-dependent folding and aggregation structural changes of HGD and HGD P23T. Results When the temperature was below 70 ℃, the barycentric mean of the intrinsic fluorescence of HGD and HGD P23T shifted towards a longer wavelength with increasing temperature and the fluorescence intensity decreased indicating the unfolded protein conformations. The conformational stability of HGD P23T was weaker than that of HGD. When temperature was higher than 70 ℃, the static light scattering intensity increased significantly with temperature, indicating protein aggregation upon heating. Relative to the wild-type,HGD P23T showed a stronger aggregation potency. Conclusions Heating disrupts the folding conformation of γD-crystallin, induces the unfolded protein to aggregate. The disease-associated P23T mutation significantly reduces the conformational stability of γD-crystallin.
format Article
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institution OA Journals
issn 1001-6325
language zho
publishDate 2025-01-01
publisher Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
record_format Article
series Jichu yixue yu linchuang
spelling doaj-art-b31c392bd8b248dcb630430708fa70032025-08-20T01:50:33ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252025-01-014511610.16352/j.issn.1001-6325.2025.01.0001Heat-induced denaturation of cataract-related human γD-crystallinZHOU Xin, LI Zhenyan, LI Shuyuan, ZHANG Wenbo, WANG Chenxuan0Department of Biophysics and Structural Biology, State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, ChinaObjective To reveal the thermally induced denaturation of wild-type human γD-crystallin(HGD) and congenital cataract-related mutant (HGD P23T), and compare the differences in the structural changes between wild-type and mutants during a heating process. Methods HGD and HGD P23T were expressed and purified. The temperature-dependent intrinsic fluorescence intensity and static light scattering intensity of the protein samples were measured to reveal the temperature-dependent folding and aggregation structural changes of HGD and HGD P23T. Results When the temperature was below 70 ℃, the barycentric mean of the intrinsic fluorescence of HGD and HGD P23T shifted towards a longer wavelength with increasing temperature and the fluorescence intensity decreased indicating the unfolded protein conformations. The conformational stability of HGD P23T was weaker than that of HGD. When temperature was higher than 70 ℃, the static light scattering intensity increased significantly with temperature, indicating protein aggregation upon heating. Relative to the wild-type,HGD P23T showed a stronger aggregation potency. Conclusions Heating disrupts the folding conformation of γD-crystallin, induces the unfolded protein to aggregate. The disease-associated P23T mutation significantly reduces the conformational stability of γD-crystallin.https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-1-1.pdfcrystallin|thermal stability|aggregation|intrinsic fluorescence|static light scattering
spellingShingle ZHOU Xin, LI Zhenyan, LI Shuyuan, ZHANG Wenbo, WANG Chenxuan
Heat-induced denaturation of cataract-related human γD-crystallin
Jichu yixue yu linchuang
crystallin|thermal stability|aggregation|intrinsic fluorescence|static light scattering
title Heat-induced denaturation of cataract-related human γD-crystallin
title_full Heat-induced denaturation of cataract-related human γD-crystallin
title_fullStr Heat-induced denaturation of cataract-related human γD-crystallin
title_full_unstemmed Heat-induced denaturation of cataract-related human γD-crystallin
title_short Heat-induced denaturation of cataract-related human γD-crystallin
title_sort heat induced denaturation of cataract related human γd crystallin
topic crystallin|thermal stability|aggregation|intrinsic fluorescence|static light scattering
url https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-1-1.pdf
work_keys_str_mv AT zhouxinlizhenyanlishuyuanzhangwenbowangchenxuan heatinduceddenaturationofcataractrelatedhumangdcrystallin