7D9N

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

Summary for 7D9N

• Entry DOI: 10.2210/pdb7d9n/pdb
• Descriptor: Lamin-A/C (1 entity in total)
• Functional Keywords: nuclear lamin a/c, lamin s143f, intermediate filament, hgps, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 47331.01

Authors

Ahn, J.,Jung, S.,Ha, N. (deposition date: 2020-10-14, release date: 2021-11-17, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.7 Å)