Cellular Sodium-Calcium Exchange Illuminated

A clearer picture of how cells traffic calcium comes from a new structure of a membrane ion-exchange protein (Science, DOI: 10.1126/science.1215759). Cellular calcium transport is essential for processes including fertilization, muscle contraction, and cell death. A group led by Youxing Jiang, a Howard Hughes Medical Institute investigator at the University of Texas Southwestern Medical Center, crystallized and solved the structure of an archaeal Na⁺/Ca²⁺ exchanger (NCX). The protein is homologous to eukaryotic transport proteins that exchange three Na⁺ ions for one Ca²⁺ ion across cell membranes. The group found that NCX is made up of a bundle of 10 helices that span a membrane and enclose a central cation-binding pocket. The researchers propose a “helix sliding” conformational mechanism for ion exchange that alternately opens ion channels to the interior and exterior of a cell, with Na⁺ and Ca²⁺ ions competing for ligands in the binding pocket. The structure generally confirms what scientists had learned about eukaryotic exchangers through other methods. The archaeal protein, however, does not include a regulatory domain found in eukaryotic exchangers, so interactions between the regulatory and transport domains remain to be clarified.