Structural dynamics of Na⁺ and Ca²⁺ interactions with full-size mammalian NCX.

ABSTRACT: Cytosolic Ca²⁺ and Na⁺ allosterically regulate Na⁺/Ca²⁺ exchanger (NCX) proteins to vary the NCX-mediated Ca²⁺ entry/exit rates in diverse cell types. To resolve the structure-based dynamic mechanisms underlying the ion-dependent allosteric regulation in mammalian NCXs, we analyze the apo, Ca²⁺, and Na⁺-bound species of the brain NCX1.4 variant using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics (MD) simulations. Ca²⁺ binding to the cytosolic regulatory domains (CBD1 and CBD2) rigidifies the intracellular regulatory loop (5L6) and promotes its interaction with the membrane domains. Either Na⁺ or Ca²⁺ stabilizes the intracellular portions of transmemb

SUBMITTER: Giladi M 

PROVIDER: S-EPMC11021524 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature