{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T23:03:07Z","timestamp":1778281387650,"version":"3.51.4"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Cataract, opacity of the eye lens, is the leading cause of visual impairment worldwide. The crucial pathogenic factors that cause cataract are misfolding and aggregation of crystallin protein. \u03b2B1\u2010crystallin, which is the most abundant water\u2010soluble protein in mammalian lens, is essential for lens transparency. A previous study identified the missense mutation \u03b2B1\u2010S93R being responsible for congenital cataract. However, the exact pathogenic mechanism causing cataract remains unclear. The S93 residue, which is located at the first Greek\u2010key motif of \u03b2B1\u2010crystallin, is highly conserved, and its substitution to Arginine severely impaired hydrogen bonds and structural conformation, which were evaluated <jats:italic>via<\/jats:italic> Molecular Dynamic Simulation. The \u03b2B1\u2010S93R was also found to be prone to aggregation in both human cell lines and <jats:italic>Escherichia coli<\/jats:italic>. Then, we isolated the \u03b2B1\u2010S93R variant from inclusion bodies by protein renaturation. The \u03b2B1-S93R mutation exposed more hydrophobic residues, and the looser structural mutation was prone to aggregation. Furthermore, the S93R mutation reduced the structural stability of \u03b2B1-crystallin when incubated at physiological temperature and made it more sensitive to environmental stress, such as UV irradiation or oxidative stress. We also constructed a \u03b2B1-S93R cellular model and discovered that \u03b2B1-S93R was more sensitive to environmental stress, causing not only aggregate formation but also cellular apoptosis and impaired cellular viability. All of the results indicated that lower solubility and structural stability, sensitivity to environmental stress, vulnerability to aggregation, and impaired cellular viability of \u03b2B1-S93R might be involved in cataract development.<\/jats:p>","DOI":"10.3389\/fmolb.2022.844719","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T08:58:42Z","timestamp":1647248322000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Cataract-Causing S93R Mutant Destabilized Structural Conformation of \u03b2B1 Crystallin Linking With Aggregates Formation and Cellular Viability"],"prefix":"10.3389","volume":"9","author":[{"given":"Ling","family":"Ren","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanyue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangjun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yibo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.ijbiomac.2017.05.048","article-title":"Protein Aggregation: From Background to Inhibition Strategies","volume":"103","author":"Alam","year":"2017","journal-title":"Int. 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