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Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation
Lamins are intermediate filaments that form a 3-D meshwork in the periphery of the nuclear envelope. 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 caus...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956589/ https://www.ncbi.nlm.nih.gov/pubmed/35338226 http://dx.doi.org/10.1038/s42003-022-03212-3 |
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author | Ahn, Jinsook Jeong, Soyeon Kang, So-mi Jo, Inseong Park, Bum-Joon Ha, Nam-Chul |
author_facet | Ahn, Jinsook Jeong, Soyeon Kang, So-mi Jo, Inseong Park, Bum-Joon Ha, Nam-Chul |
author_sort | Ahn, Jinsook |
collection | PubMed |
description | Lamins are intermediate filaments that form a 3-D meshwork in the periphery of the nuclear envelope. 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. |
format | Online Article Text |
id | pubmed-8956589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89565892022-04-20 Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation Ahn, Jinsook Jeong, Soyeon Kang, So-mi Jo, Inseong Park, Bum-Joon Ha, Nam-Chul Commun Biol Article Lamins are intermediate filaments that form a 3-D meshwork in the periphery of the nuclear envelope. 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. Nature Publishing Group UK 2022-03-25 /pmc/articles/PMC8956589/ /pubmed/35338226 http://dx.doi.org/10.1038/s42003-022-03212-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ahn, Jinsook Jeong, Soyeon Kang, So-mi Jo, Inseong Park, Bum-Joon Ha, Nam-Chul Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation |
title | Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation |
title_full | Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation |
title_fullStr | Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation |
title_full_unstemmed | Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation |
title_short | Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation |
title_sort | crystal structure of progeria mutant s143f lamin a/c reveals increased hydrophobicity driving nuclear deformation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8956589/ https://www.ncbi.nlm.nih.gov/pubmed/35338226 http://dx.doi.org/10.1038/s42003-022-03212-3 |
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