Opposing Intermolecular Tuning of Ca²⁺ Affinity for Calmodulin by Neurogranin and CaMKII Peptides.

ABSTRACT: We investigated the impact of bound calmodulin (CaM)-target compound structure on the affinity of calcium (Ca²⁺) by integrating coarse-grained models and all-atomistic simulations with nonequilibrium physics. We focused on binding between CaM and two specific targets, Ca²⁺/CaM-dependent protein kinase II (CaMKII) and neurogranin (Ng), as they both regulate CaM-dependent Ca²⁺ signaling pathways in neurons. It was shown experimentally that Ca²⁺/CaM (holoCaM) binds to the CaMKII peptide with overwhelmingly higher affinity than Ca²⁺-free CaM (apoCaM); the binding of CaMKII peptide to CaM in return increases the Ca²⁺ affinity for CaM. However, this reciprocal relation was not observed in the Ng peptide (Ng_13-49), which

SUBMITTER: Zhang P 

PROVIDER: S-EPMC5374985 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature