An Ancestral Mechanism of Calmodulin Binding to Cds1 Kinase Inhibits Catalytic Activity

Manovella, SA; Wang, T; Young, SN; Dite, TA; Vaibhav, V; Binos, S; Dagley, LF; Nguyen, ATN; Means, AR; Petersen, J; Scott, JW; Murphy, JM; Horne, CR

Author(s): Manovella, SA; Wang, T; Young, SN; Dite, TA; Vaibhav, V; Binos, S; Dagley, LF; Nguyen, ATN; Means, AR; Petersen, J; Scott, JW; Murphy, JM; Horne, CR;
Details: Publication Year 2026-08,Volume 78,Issue #8,Page e70128
Journal Title: IUBMB Life
Abstract: Calmodulin is a highly conserved, calcium (Ca(2+)) sensor protein that is ubiquitous among eukaryotes. Ca(2+) binding to Calmodulin induces a conformational change that facilitates interaction with, and activation of, serine/threonine protein kinases, including members of the CaMK family. Recently, Ca(2+)-Calmodulin binding to one such protein kinase, Checkpoint kinase 2 (CHK2), which is responsible for the regulation of cell cycle progression following DNA damage in mammalian cells, was shown to suppress CHK2 catalytic activity. Here, by applying biochemical, structural mass spectrometry and yeast genetic methods, we identify an analogous mode of inhibition of the fission yeast Schizosaccharomyces pombe CHK2 functional orthologue, Cds1, through direct binding of Ca(2+)-Calmodulin to the Cds1 kinase domain. Our studies assert an ancestral function for Calmodulin in suppressing the catalytic activity of CHK2 orthologs and highlight a mechanism by which Ca(2+) flux can attenuate Cds1 catalytic activity to facilitate exit from the replication checkpoint and promote cell cycle progression.
Publisher: IUBMB
Keywords: *Schizosaccharomyces pombe Proteins/metabolism/genetics/chemistry; *Schizosaccharomyces/metabolism/genetics/enzymology; *Checkpoint Kinase 2/metabolism/genetics/chemistry; *Calmodulin/metabolism/chemistry/genetics; Calcium/metabolism; Protein Binding; Cell Cycle
Research Division(s): Inflammation; Advanced Technology and Biology
PubMed ID: 42655879
Publisher's Version: https://doi.org/10.1002/iub.70128
Open Access at Publisher's Site: https://doi.org/10.1002/iub.70128
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-09-07 09:09:47

Last Modified: 2026-09-07 09:09:58