| Title: | Structural basis for alternating access of a eukaryotic calcium/proton exchanger |
| Author(s): | Waight AB; Pedersen BP; Schlessinger A; Bonomi M; Chau BH; Roe-Zurz Z; Risenmay AJ; Sali A; Stroud RM; |
| Address: | "Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA" |
| ISSN/ISBN: | 1476-4687 (Electronic) 0028-0836 (Print) 0028-0836 (Linking) |
| Abstract: | "Eukaryotic Ca(2+) regulation involves sequestration into intracellular organelles, and expeditious Ca(2+) release into the cytosol is a hallmark of key signalling transduction pathways. Bulk removal of Ca(2+) after such signalling events is accomplished by members of the Ca(2+):cation (CaCA) superfamily. The CaCA superfamily includes the Na(+)/Ca(2+) (NCX) and Ca(2+)/H(+) (CAX) antiporters, and in mammals the NCX and related proteins constitute families SLC8 and SLC24, and are responsible for the re-establishment of Ca(2+) resting potential in muscle cells, neuronal signalling and Ca(2+) reabsorption in the kidney. The CAX family members maintain cytosolic Ca(2+) homeostasis in plants and fungi during steep rises in intracellular Ca(2+) due to environmental changes, or following signal transduction caused by events such as hyperosmotic shock, hormone response and response to mating pheromones. The cytosol-facing conformations within the CaCA superfamily are unknown, and the transport mechanism remains speculative. Here we determine a crystal structure of the Saccharomyces cerevisiae vacuolar Ca(2+)/H(+) exchanger (Vcx1) at 2.3 A resolution in a cytosol-facing, substrate-bound conformation. Vcx1 is the first structure, to our knowledge, within the CAX family, and it describes the key cytosol-facing conformation of the CaCA superfamily, providing the structural basis for a novel alternating access mechanism by which the CaCA superfamily performs high-throughput Ca(2+) transport across membranes" |
| Keywords: | "Amino Acid Sequence Antiporters/*chemistry/*metabolism Binding Sites Calcium/*metabolism Crystallography, X-Ray Cytosol/*metabolism Ion Transport Methanococcus/chemistry Models, Molecular Molecular Sequence Data Protein Conformation Protein Folding *Proto;" |
| Notes: | "MedlineWaight, Andrew B Pedersen, Bjorn Panyella Schlessinger, Avner Bonomi, Massimiliano Chau, Bryant H Roe-Zurz, Zygy Risenmay, Aaron J Sali, Andrej Stroud, Robert M eng R37 GM024485/GM/NIGMS NIH HHS/ R01 GM024485/GM/NIGMS NIH HHS/ U01 GM61390/GM/NIGMS NIH HHS/ T32 GM008284/GM/NIGMS NIH HHS/ GM073210/GM/NIGMS NIH HHS/ GM24485/GM/NIGMS NIH HHS/ U54 GM094625/GM/NIGMS NIH HHS/ U01 GM061390/GM/NIGMS NIH HHS/ U19 GM061390/GM/NIGMS NIH HHS/ P50 GM073210/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2013/05/21 Nature. 2013 Jul 4; 499(7456):107-10. doi: 10.1038/nature12233. Epub 2013 May 19" |
