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Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation
Cited 2 time in
Web of Science
Cited 3 time in Scopus
- Authors
- Issue Date
- 2022-12
- Publisher
- Nature Publishing Group
- Citation
- Communications Biology, Vol.5 No.1, p. 267
- Abstract
- 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. Increased hydrophobicity identified by the crystal structure presented in this work suggests a mechanism by which the S143F form of lamin A/C leads to progeria, a rapid aging syndrome. The authors observed aberrant molecular interactions that appear to lead to the nuclear deformation seen in other progeroid syndromes.
- ISSN
- 2399-3642
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