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Structural basis for the interaction between unfarnesylated progerin and the Ig-like domain of lamin A/C in premature aging disorders
Cited 2 time in
Web of Science
Cited 3 time in Scopus
- Authors
- Issue Date
- 2022-12
- Publisher
- Elsevier B.V.
- Citation
- Biochemical and Biophysical Research Communications, Vol.637, pp.210-217
- Abstract
- © 2022 Elsevier Inc.Hutchinson–Gilford progeria syndrome (HGPS) is a premature aging disorder caused by C-terminally truncated lamin A, termed as the pre-progerin product. Progerin is a C-terminally farnesylated protein derived from pre-progerin, which causes nuclear deformation at the inner-nuclear membrane. As an alternative or additional mechanism, a farnesylation-independent abnormal interaction between the C-terminus of progerin and Ig-like domain has been proposed. However, the molecular mechanism underlying the role of unfarnesylated C-terminus of pre-progerin in HGPS remains largely unknown. In this study, we determined the crystal structures of C-terminal peptide of progerin and Ig-like domain of lamin A/C. Results showed that the C-terminal cysteine residue of progerin forms a disulfide bond with the only cysteine residue of the Ig-like domain. This finding suggested that unfarnesylated progerin can form a disulfide bond with the Ig-like domain in the lamin meshwork. The Alphafold2-assisted docking structure showed that disulfide bond formation was promoted by a weak interaction between the groove of Ig-like domain and the unfarnesylated C-terminal tail region of progerin. Our results provide molecular insights into the normal aging process as well as premature aging of humans.
- ISSN
- 0006-291X
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