Basic and editing mechanisms underlying ion transport and regulation in NCX variants

Research output: Contribution to journalArticlepeer-review


Structure-dynamic analysis of archaeal NCX (NCX_Mj) provided new insights into the underlying mechanisms of ion selectivity, ion-coupled alternating access, ion occlusion, and transport catalysis. This knowledge is relevant, not only for prokaryotic and eukaryotic NCXs, but also for other families belonging to the superfamily of Ca2+/CA antiporters. In parallel with the ion transport mechanisms, the structure-dynamic determinants of regulatory CBD1 and CBD2 domains have been resolved according to which the Ca2+-induced allosteric signal is decoded at the two-domain interface and “secondarily” modified by a splicing segment at CBD2. The exon-dependent combinations within the splicing segment control the number of Ca2+ binding sites (from zero to three) at CBD2, as well as the Ca2+ binding affinity and Ca2+ off-rates at both CBDs. The exon-dependent combinations specifically rigidify the local segments at CBDs, yielding the Ca2+-dependent activation (through Ca2+ binding to CBD1) and Ca2+-dependent alleviation of Na+-induced inactivation (through Ca2+ binding with CBD2). The exon-dependent synergistic interactions between CBDs characteristically differ in NCX1 and NCX3, thereby underscoring the physiological relevance of structure-controlled shaping of ion-dependent regulation in tissue-specific NCX variants. How the ion-dependent regulatory modules operate in conjunction with other regulators (PIP2, palmitoylation, XIP, among the others) of NCX is an open question that remains to be determined.

Original languageEnglish
Article number102131
JournalCell Calcium
StatePublished - Jan 2020


  • Allosteric regulation
  • Alternating access
  • Alternative splicing
  • Antiporter
  • Ion selectivity
  • Ion transport mechanisms
  • NCX
  • Naand Ca binding sites
  • Sodium-calcium exchanger


Dive into the research topics of 'Basic and editing mechanisms underlying ion transport and regulation in NCX variants'. Together they form a unique fingerprint.

Cite this