{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:59:41Z","timestamp":1760623181588,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K08AR070290","R03AR076484"],"award-info":[{"award-number":["K08AR070290","R03AR076484"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Keratin intermediate filaments constitute the primary cytoskeletal component of epithelial cells. Numerous human disease phenotypes related to keratin mutation remain mechanistically elusive. Our recent crystal structures of the helix 1B heterotetramer from keratin 1\/10 enabled further investigation of the effect of pathologic 1B domain mutations on keratin structure. We used our highest resolution keratin 1B structure as a template for homology-modeling the 1B heterotetramers of keratin 5\/14 (associated with blistering skin disorders), keratin 8\/18 (associated with liver disease), and keratin 74\/28 (associated with hair disorder). Each structure was examined for the molecular alterations caused by incorporating pathogenic 1B keratin mutations. Structural modeling indicated keratin 1B mutations can harm the heterodimer interface (R265PK5, L311RK5, R211PK14, I150VK18), the tetramer interface (F231LK1, F274SK74), or higher-order interactions needed for mature filament formation (S233LK1, L311RK5, Q169EK8, H128LK18). The biochemical changes included altered hydrophobic and electrostatic interactions, and altered surface charge, hydrophobicity or contour. Together, these findings advance the genotype-structurotype-phenotype correlation for keratin-based human diseases.<\/jats:p>","DOI":"10.3390\/ijms21186641","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T22:58:01Z","timestamp":1599778681000},"page":"6641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular Modeling of Pathogenic Mutations in the Keratin 1B Domain"],"prefix":"10.3390","volume":"21","author":[{"given":"Alexander J.","family":"Hinbest","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Wesleyan University, Middletown, CT 06459, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherif A.","family":"Eldirany","sequence":"additional","affiliation":[{"name":"Yale School of Medicine, Yale University, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-3919","authenticated-orcid":false,"given":"Minh","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-8308","authenticated-orcid":false,"given":"Christopher G.","family":"Bunick","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Yale University, New Haven, CT 06520, USA"},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"ref_1","first-page":"1108","article-title":"The cytoskeleton of digestive epithelia in health and disease","volume":"277","author":"Ku","year":"1999","journal-title":"Am. 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