Structure-based dynamic arrays in regulatory domains of sodium-calcium exchanger (NCX) isoforms.

ABSTRACT: Mammalian Na⁺/Ca²⁺ exchangers, NCX1 and NCX3, generate splice variants, whereas NCX2 does not. The CBD1 and CBD2 domains form a regulatory tandem (CBD12), where Ca²⁺ binding to CBD1 activates and Ca²⁺ binding to CBD2 (bearing the splicing segment) alleviates the Na⁺-induced inactivation. Here, the NCX2-CBD12, NCX3-CBD12-B, and NCX3-CBD12-AC proteins were analyzed by small-angle X-ray scattering (SAXS) and hydrogen-deuterium exchange mass-spectrometry (HDX-MS) to resolve regulatory variances in the NCX2 and NCX3 variants. SAXS revealed the unified model, according to which the Ca²⁺ binding to CBD12 shifts a dynamic equilibrium without generating new conformational states, and where more rigid conformational states become more

SUBMITTER: Giladi M 

PROVIDER: S-EPMC5430519 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature