7D9N

Crystal structure of a non-canonic progeria mutation S143F at lamin A/C and its structural implication to the premature aging

7D9N の概要

• エントリーDOI: 10.2210/pdb7d9n/pdb
• 分子名称: Lamin-A/C (1 entity in total)
• 機能のキーワード: nuclear lamin a/c, lamin s143f, intermediate filament, hgps, structural protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47331.01

構造登録者

Ahn, J.,Jung, S.,Ha, N. (登録日: 2020-10-14, 公開日: 2021-11-17, 最終更新日: 2024-10-23)

主引用文献

Ahn, J.,Jeong, S.,Kang, S.M.,Jo, I.,Park, B.J.,Ha, N.C.
Crystal structure of progeria mutant S143F lamin A/C reveals increased hydrophobicity driving nuclear deformation.
Commun Biol, 5:267-267, 2022

PubMed 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.

PubMed: 35338226
DOI: 10.1038/s42003-022-03212-3

実験手法

X-RAY DIFFRACTION (3.7 Å)