Dynamic Na⁺/H⁺ exchanger 1 (NHE1) - calmodulin complexes of varying stoichiometry and structure regulate Ca²⁺-dependent NHE1 activation.

ABSTRACT: Calmodulin (CaM) engages in Ca²⁺-dependent interactions with numerous proteins, including a still incompletely understood physical and functional interaction with the human Na⁺/H⁺-exchanger NHE1. Using nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry, and fibroblasts stably expressing wildtype and mutant NHE1, we discovered multiple accessible states of this functionally important complex existing in different NHE1:CaM stoichiometries and structures. We determined the NMR solution structure of a ternary complex in which CaM links two NHE1 cytosolic tails. In vitro, stoichiometries and affinities could be tuned by variations in NHE1:CaM ratio and calcium ([Ca²⁺]) and by phosphorylation of S648 in the first CaM

SUBMITTER: Sjogaard-Frich LM 

PROVIDER: S-EPMC8009664 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature