{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:37:12Z","timestamp":1782779832933,"version":"3.54.5"},"reference-count":54,"publisher":"Portland Press Ltd.","issue":"14","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,7,15]]},"abstract":"<jats:p>The high solubility and lifelong stability of crystallins are crucial to the maintenance of lens transparency and optical properties. Numerous crystallin mutations have been linked to congenital cataract, which is one of the leading causes of newborn blindness. Besides cataract, several crystallin mutations have also been linked to syndromes such as congenital microcornea-cataract syndrome (CMCC). However, the molecular mechanism of CMCC caused by crystallin mutations remains elusive. In the present study, we investigated the mechanism of CMCC caused by the X253R mutation in \u03b2B1-crystallin. The exogenously expressed X253R proteins were prone to form p62-negative aggregates in HeLa cells, strongly inhibited cell proliferation and induced cell apoptosis. The intracellular X253R aggregates could be successfully redissolved by lanosterol but not cholesterol. The extra 26 residues at the C-terminus of \u03b2B1-crystallin introduced by the X253R mutation had little impact on \u03b2B1-crystallin structure and stability, but increased \u03b2B1-crystallin hydrophobicity and decreased its solubility. Interestingly, the X253R mutant fully abolished the aggregatory propensity of \u03b2B1- and \u03b2A3\/\u03b2B1-crystallins at high temperatures, suggesting that X253R was an aggregation-inhibition mutation of \u03b2-crystallin homomers and heteromers in dilute solutions. Our results suggest that an increase in hydrophobicity and a decrease in solubility might be responsible for cataractogenesis induced by the X253R mutation, while the cytotoxic effect of X253R aggregates might contribute to the defects in ocular development. Our results also highlight that, at least in some cases, the aggregatory propensity in dilute solutions could not fully mimic the behaviours of mutated proteins in the crowded cytoplasm of the cells.<\/jats:p>","DOI":"10.1042\/bcj20160247","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T02:35:39Z","timestamp":1463020539000},"page":"2087-2096","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Congenital microcornea-cataract syndrome-causing mutation X253R increases \u03b2B1-crystallin hydrophobicity to promote aggregate formation"],"prefix":"10.1042","volume":"473","author":[{"given":"Xiao-Yao","family":"Leng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Yun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Bo","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Bo","family":"Xi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Bin","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,7,12]]},"reference":[{"key":"2021112216281439100_B1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.pbiomolbio.2003.11.012","article-title":"Ageing and vision: structure, stability and function of lens crystallins","volume":"86","author":"Bloemendal","year":"2004","journal-title":"Prog. 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