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The recent crystal structure of a long fragment of human lamin A\/C visualized the tetrameric assembly unit of the central rod domain as a polymerization intermediate. A genetic mutation of S143F caused a phenotype characterized by both progeria and muscular dystrophy. In this study, we determined the crystal structure of the lamin A\/C fragment harboring the S143F mutation. The obtained structure revealed the X-shaped interaction between the tetrameric units in the crystals, potentiated by the hydrophobic interactions of the mutated Phe143 residues. Subsequent studies indicated that the X-shaped interaction between the filaments plays a crucial role in disrupting the normal lamin meshwork. Our findings suggest the assembly mechanism of the 3-D meshwork and further provide a molecular framework for understanding the aging process by nuclear deformation.<\/jats:p>","DOI":"10.1038\/s42003-022-03212-3","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T11:03:05Z","timestamp":1648206185000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Crystal structure of progeria mutant S143F lamin A\/C reveals increased hydrophobicity driving nuclear deformation"],"prefix":"10.1038","volume":"5","author":[{"given":"Jinsook","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyeon","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-mi","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inseong","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6037-7219","authenticated-orcid":false,"given":"Bum-Joon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-748X","authenticated-orcid":false,"given":"Nam-Chul","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"3212_CR1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1006\/jsbi.1998.3987","volume":"122","author":"N Stuurman","year":"1998","unstructured":"Stuurman, N., Heins, S. & Aebi, U. 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