Disruption of Ca²⁺/calmodulin:KSR1 interaction lowers ERK activation.

ABSTRACT: KSR1, a key scaffold protein for the MAPK pathway, facilitates ERK activation upon growth factor stimulation. We recently demonstrated that KSR1 binds the Ca²⁺-binding protein calmodulin (CaM), thereby providing an intersection between KSR1-mediated and Ca²⁺ signaling. In this study, we set out to generate a KSR1 point mutant with reduced Ca²⁺/CaM binding in order to unravel the functional implications of their interaction. To do so, we solved the structural determinants of complex formation. Using purified fragments of KSR1, we showed that Ca²⁺/CaM binds to the CA3 domain of KSR1. We then used in silico molecular modeling to predict contact residues for binding. This approach identified two possible modes of interaction: (1) binding of extended

SUBMITTER: Thines L 

PROVIDER: S-EPMC11002989 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature