Delineation of the CENP-LN sub-complex dissociation mechanism upon multisite phosphorylation during mitosis

Phosphorylation is the most prevalent form of regulation in cells, organizing virtually all cellular functions, including survival, motility, differentiation, proliferation, and metabolism. This regulatory function has been largely conserved from the primitive single-cell to the more complex multice...

Full description

Saved in:
Bibliographic Details
Published in:Journal of biomolecular structure & dynamics 2024-11, Vol.42 (17), p.8983-9001
Main Author: Durojaye, Olanrewaju Ayodeji
Format: Article
Language:English
Subjects:
CCAN
CENP-L
CENP-N
Chromosomal Proteins, Non-Histone - chemistry
Chromosomal Proteins, Non-Histone - metabolism
Humans
Kinetochores - chemistry
Kinetochores - metabolism
Mitosis
Molecular Dynamics Simulation
Phosphorylation
Posttranslational modification
Protein Binding
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Phosphorylation is the most prevalent form of regulation in cells, organizing virtually all cellular functions, including survival, motility, differentiation, proliferation, and metabolism. This regulatory function has been largely conserved from the primitive single-cell to the more complex multicellular organisms. More than a third of proteins in eukaryotes are phosphorylated, and essentially every class of protein undergoes regulation by phosphorylation. A decline in the cellular level of CENP-L and CENP-N (components of the constitutive centromere associated network) has earlier been reported and linked to cyclin-dependent kinase (CDK) phosphorylation upon transition into mitosis. Given the importance of posttranslational modifications in cell cycle regulation, mechanistic comprehension of the impact of phosphorylation on both proteins (CENP-L and CENP-N) is of high significance. Through the application of diverse computational analytical techniques, including atomistic molecular dynamics simulations, the mechanism of kinetochore mis-localization and dissociation of the CENP-LN sub-complex in mitosis was delineated. We showed that the phosphorylation of both components of the sub-complex induces global conformational destabilizing effects on the proteins, combined with changes in the electrostatic potential and increase in steric clashes around the protein-protein interaction interface. This, consistent with earlier experimental reports, suggest that the multisite phosphorylation of the CENP-LN sub-complex plays a crucial role in the regulation of cell division. Communicated by Ramaswamy H. Sarma
ISSN:0739-1102
1538-0254
1538-0254
DOI:10.1080/07391102.2023.2249101