Chauhan, PK and Sowdhamini, R (2023) Computational analysis of the flexibility in the disordered linker region connecting LIM domains in cysteine–glycine-rich protein. In: Frontiers in Genetics, 14 .
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Abstract
One of the key proteins that are present in the Z-disc of cardiac tissues, CSRP3, has been implicated in dilated and hypertrophic cardiomyopathy leading to heart failure. Although multiple cardiomyopathy-related mutations have been reported to reside on the two LIM domains and the disordered regions connecting the domains in this protein, the exact role of the disordered linker region is not clear. The linker harbors a few post-translational modification sites and is expected to be a regulatory site. We have carried out evolutionary studies on 5614 homologs spanning across taxa. We also performed molecular dynamics simulations of full-length CSRP3 to show that the length variations and conformational flexibility of the disordered linker could provide additional levels of functional modulation. Finally, we show that the CSRP3 homologs with widely different lengths of the linker regions could display diversity in their functional specifications. The present study provides a useful perspective to our understanding of the evolution of the disordered region between CSRP3 LIM domains. Copyright © 2023 Chauhan and Sowdhamini.
| Item Type: | Journal Article |
|---|---|
| Publication: | Frontiers in Genetics |
| Publisher: | Frontiers Media S.A. |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | cardiomyopathy; CSRP3; disordered region; molecular dynamics; PPI |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 19 May 2023 07:10 |
| Last Modified: | 19 May 2023 07:10 |
| URI: | https://eprints.iisc.ac.in/id/eprint/81572 |
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