Key result
Binding of Ca2+ to CBD1 and CBD2 domains regulates ion transport in the Na+/Ca2+ exchanger, with alternative splicing in CBD2 modulating Ca2+ affinities in both domains.
This study elucidates the molecular mechanism by which Ca2+ binding to CBD1 and CBD2 regulates the Na+/Ca2+ exchanger, highlighting the role of alternative splicing in modulating binding affinities.
No immediate clinical implications; leaves open whether CBD2 splicing modulates NCX function in human disease.
The binding of Ca(2+) to two adjacent Ca(2+)-binding domains, CBD1 and CBD2, regulates ion transport in the Na(+)/Ca(2+) exchanger. As sensors for intracellular Ca(2+), the CBDs form electrostatic switches that induce the conformational changes required to initiate and sustain Na(+)/Ca(2+) exchange. Depending on the presence of a few key residues in the Ca(2+)-binding sites, zero to four Ca(2+) ions can bind with affinities between 0.1 to 20 μm. Importantly, variability in CBD2 as a consequence of alternative splicing modulates not only the number and affinities of the Ca(2+)-binding sites in CBD2 but also the Ca(2+) affinities in CBD1.
No takes yet. Share an insight, caveat, or question.
M. Hilge (2012) reported a review. Binding of Ca2+ to CBD1 and CBD2 domains regulates ion transport in the Na+/Ca2+ exchanger, with alternative splicing in CBD2 modulating Ca2+ affinities in both domains.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: