Mechanistic insights into the role of calcium in the allosteric regulation of the calmodulin-regulated death-associated protein kinase.

ABSTRACT: Calcium (Ca²⁺) signaling plays an important role in the regulation of many cellular functions. Ca²⁺-binding protein calmodulin (CaM) serves as a primary effector of calcium function. Ca²⁺/CaM binds to the death-associated protein kinase 1 (DAPK1) to regulate intracellular signaling pathways. However, the mechanism underlying the influence of Ca²⁺ on the conformational dynamics of the DAPK1-CaM interactions is still unclear. Here, we performed large-scale molecular dynamics (MD) simulations of the DAPK1-CaM complex in the Ca²⁺-bound and-unbound states to reveal the importance of Ca²⁺. MD simulations revealed that removal of Ca²⁺ increased the anti-correlated inter-domain motions between DAPK1 and CaM, which weakene

SUBMITTER: Li X 

PROVIDER: S-EPMC9806222 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature