{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:40:07Z","timestamp":1791045607033,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31872724"],"award-info":[{"award-number":["31872724"]}]},{"name":"National Natural Science Foundation of China","award":["81900837"],"award-info":[{"award-number":["81900837"]}]},{"name":"National Natural Science Foundation of China","award":["82171033"],"award-info":[{"award-number":["82171033"]}]},{"name":"National Natural Science Foundation of China","award":["81970781"],"award-info":[{"award-number":["81970781"]}]},{"name":"National Natural Science Foundation of China","award":["LD21H120001"],"award-info":[{"award-number":["LD21H120001"]}]},{"name":"National Natural Science Foundation of China","award":["LR21H120001"],"award-info":[{"award-number":["LR21H120001"]}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["31872724"],"award-info":[{"award-number":["31872724"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["81900837"],"award-info":[{"award-number":["81900837"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["82171033"],"award-info":[{"award-number":["82171033"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["81970781"],"award-info":[{"award-number":["81970781"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LD21H120001"],"award-info":[{"award-number":["LD21H120001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LR21H120001"],"award-info":[{"award-number":["LR21H120001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Zhejiang Province for Distinguished Young Scholar","award":["31872724"],"award-info":[{"award-number":["31872724"]}]},{"name":"Natural Science Foundation of Zhejiang Province for Distinguished Young Scholar","award":["81900837"],"award-info":[{"award-number":["81900837"]}]},{"name":"Natural Science Foundation of Zhejiang Province for Distinguished Young Scholar","award":["82171033"],"award-info":[{"award-number":["82171033"]}]},{"name":"Natural Science Foundation of Zhejiang Province for Distinguished Young Scholar","award":["81970781"],"award-info":[{"award-number":["81970781"]}]},{"name":"Natural Science Foundation of Zhejiang Province for Distinguished Young Scholar","award":["LD21H120001"],"award-info":[{"award-number":["LD21H120001"]}]},{"name":"Natural Science Foundation of Zhejiang Province for Distinguished Young Scholar","award":["LR21H120001"],"award-info":[{"award-number":["LR21H120001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Congenital cataracts account for approximately 5\u201320% of childhood blindness worldwide and 22\u201330% of childhood blindness in developing countries. Genetic disorders are the primary cause of congenital cataracts. In this work, we investigated the underlying molecular mechanism of G149V point missense mutation in \u03b2B2-crystallin, which was first identified in a three-generation Chinese family with two affected members diagnosed with congenital cataracts. Spectroscopic experiments were performed to determine the structural differences between the wild type (WT) and the G149V mutant of \u03b2B2-crystallin. The results showed that the G149V mutation significantly changed the secondary and tertiary structure of \u03b2B2-crystallin. The polarity of the tryptophan microenvironment and the hydrophobicity of the mutant protein increased. The G149V mutation made the protein structure loose and the interaction between oligomers was reduced, which decreased the stability of the protein. Furthermore, we compared \u03b2B2-crystallin WT and the G149V mutant with their biophysical properties under environmental stress. We found that the G149V mutation makes \u03b2B2-crystallin more sensitive to environmental stresses (oxidative stress, UV irradiation, and heat shock) and more likely to aggregate and form precipitation. These features might be important to the pathogenesis of \u03b2B2-crystallin G149V mutant related to congenital cataracts.<\/jats:p>","DOI":"10.3390\/biom13050864","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T10:35:11Z","timestamp":1684492511000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by \u03b2B2-G149V Mutation"],"prefix":"10.3390","volume":"13","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310030, China"},{"name":"Department of Ophthalmology, Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, 158 Shangtang Road, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyue","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, 268 Kaixuan Road, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sifan","family":"Zheng","sequence":"additional","affiliation":[{"name":"GKT School of Medical Education, King\u2019s College London, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, 268 Kaixuan Road, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenqi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-3416","authenticated-orcid":false,"given":"Xiangjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310030, China"},{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, 268 Kaixuan Road, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-7419","authenticated-orcid":false,"given":"Xingchao","family":"Shentu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.47162\/RJME.61.1.11","article-title":"Congenital cataract\u2014Clinical and morphological aspects","volume":"61","author":"Costache","year":"2020","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1221","DOI":"10.1016\/S2214-109X(17)30393-5","article-title":"Global causes of blindness and distance vision impairment 1990\u20132020: A systematic review and meta-analysis","volume":"5","author":"Flaxman","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0140-6736(17)30544-5","article-title":"Cataracts","volume":"390","author":"Liu","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1136\/bjophthalmol-2019-315282","article-title":"Inherited cataracts: Molecular genetics, clinical features, disease mechanisms and novel therapeutic approaches","volume":"104","author":"Berry","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pichi, F., Lembo, A., Serafino, M., and Nucci, P. (2016). Developments in Ophthalmology, Karger International. Chapter 1\u201314.","DOI":"10.1159\/000442495"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/00055735-200402000-00003","article-title":"Genetics of childhood cataract","volume":"15","author":"Francis","year":"2004","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/humu.23395","article-title":"Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects","volume":"39","author":"Anand","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.exer.2016.06.011","article-title":"Mutations and mechanisms in congenital and age-related cataracts","volume":"156","author":"Shiels","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/13816810.2020.1737950","article-title":"A novel missense mutation in LIM2 causing isolated autosomal dominant congenital cataract","volume":"41","author":"Berry","year":"2020","journal-title":"Ophthalmic Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajo.2008.02.014","article-title":"Risk Factors for Complications after Congenital Cataract Surgery without Intraocular Lens Implantation in the First 18 Months of Life","volume":"146","author":"Kohnen","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/08820538.2013.825289","article-title":"Deprivation Amblyopia and Congenital Hereditary Cataract","volume":"28","author":"Mansouri","year":"2013","journal-title":"Semin. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.preteyeres.2006.10.003","article-title":"Crystallins in the eye: Function and pathology","volume":"26","author":"Andley","year":"2007","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1590\/S0004-27492011000200016","article-title":"The genetic and molecular basis of congenital cataract","volume":"74","author":"Santana","year":"2011","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.molmed.2012.03.005","article-title":"Protein misfolding and aggregation in cataract disease and prospects for prevention","volume":"18","author":"Moreau","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","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. Biophys. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0014-4835(03)00173-8","article-title":"The stability of human acidic \u03b2-crystallin oligomers and hetero-oligomers","volume":"77","author":"Bateman","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0014-4835(03)00159-3","article-title":"Human \u03b2-crystallins modified by backbone cleavage, deamidation and oxidation are prone to associate","volume":"77","author":"Zhang","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_18","first-page":"205","article-title":"Lens Proteomics: The Accumulation of Crystallin Modifications in the Mouse Lens with Age","volume":"43","author":"Ueda","year":"2002","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_19","first-page":"216","article-title":"Lens Proteomics: Analysis of Rat Crystallin Sequences and Two-Dimensional Electrophoresis Map","volume":"43","author":"Lampi","year":"2002","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_20","first-page":"977","article-title":"Mutations in crystallin genes result in congenital cataract associated with other ocular abnormalities","volume":"23","author":"Sun","year":"2017","journal-title":"Mol. Vis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Xu, J., Wang, S., Zhao, W.-J., Xi, Y.-B., Yan, Y.-B., and Yao, K. (2012). The congenital cataract-linked A2V mutation impairs tetramer formation and promotes aggregation of \u03b2B2-crystallin. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051200"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1002\/humu.20724","article-title":"A novel mutation in Alpha A-crystallin (CRYAA) caused autosomal dominant congenital cataract in a large Chinese family","volume":"29","author":"Gu","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/978-1-4939-1053-3_6","article-title":"Site-saturation mutagenesis by overlap extension PCR","volume":"1179","author":"Williams","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0378-1119(89)90358-2","article-title":"Site-directed mutagenesis by overlap extension using the polymerase chain reaction","volume":"77","author":"Ho","year":"1989","journal-title":"Gene"},{"key":"ref_25","first-page":"177","article-title":"Site-directed mutagenesis using overlap extension PCR","volume":"57","author":"Aiyar","year":"1996","journal-title":"Methods Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.bbrc.2020.03.072","article-title":"The cataract-related S39C variant increases gamma S-crystallin sensitivity to environmental stress by destroying the intermolecular disulfide cross-links","volume":"526","author":"Yang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.ijbiomac.2020.11.158","article-title":"Cataract-causing mutations L45P and Y46D promote \u03b3 C-crystallin aggregation by disturbing hydrogen bonds network in the second Greek key motif","volume":"167","author":"Fu","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"166018","DOI":"10.1016\/j.bbadis.2020.166018","article-title":"\u03b2B2 W151R mutant is prone to degradation, aggregation and exposes the hydrophobic side chains in the fourth Greek Key motif","volume":"1867","author":"Xu","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1021\/bi0518141","article-title":"Mini-\u03b1B-crystallin: A functional element of \u03b1B-crystallin with chaperone-like activity","volume":"45","author":"Bhattacharyya","year":"2006","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6122","DOI":"10.1021\/bi100664s","article-title":"Increase in surface hydrophobicity of the cataract-associated P23T mutant of human \u03b3D-crystallin is responsible for its dramatically lower, retrograde solubility","volume":"49","author":"Pande","year":"2010","journal-title":"Biochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1021\/bi301662w","article-title":"The \u03b1A66\u201380 peptide interacts with soluble \u03b1-crystallin and induces its aggregation and precipitation: A contribution to age-related cataract Formation","volume":"52","author":"Kannan","year":"2013","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nature14650","article-title":"Lanosterol reverses protein aggregation in cataracts","volume":"523","author":"Zhao","year":"2015","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.bpj.2012.07.002","article-title":"Chaperone-like effect of the linker on the isolated c-terminal domain of rabbit muscle creatine kinase","volume":"103","author":"Chen","year":"2012","journal-title":"Biophys. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD","volume":"26","author":"Phillips","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/pro.296","article-title":"Beta-Strand interactions at the domain interface critical for the stability of human lens gammaD-crystallin","volume":"19","author":"Das","year":"2010","journal-title":"Protein Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0014-4835(92)90100-7","article-title":"Structural studies on \u03b2H-crystallin from bovine eye lens","volume":"55","author":"Bateman","year":"1992","journal-title":"Exp. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6592","DOI":"10.1021\/bi00480a007","article-title":"Quaternary interactions in eye lens beta-crystallins: Basic and acidic subunits of beta-crystallins favor heterologous association","volume":"29","author":"Slingsby","year":"1990","journal-title":"Biochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/302415a0","article-title":"Short-range order of crystallin proteins accounts for eye lens transparency","volume":"302","author":"Delaye","year":"1983","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bbadis.2013.10.001","article-title":"The importance of the last strand at the C-terminus in \u03b2B2-crystallin stability and assembly","volume":"1842","author":"Zhang","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.1021\/bi00412a051","article-title":"Structure and stability of gamma-crystallins: Tryptophan, tyrosine, and cysteine accessibility","volume":"27","author":"Mandal","year":"1988","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.bbagen.2015.06.007","article-title":"Gamma crystallins of the human eye lens","volume":"1860","author":"Vendra","year":"2016","journal-title":"Biochim. Biophys. 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