4K1C

VCX1 Calcium/Proton Exchanger

Summary for 4K1C

• Entry DOI: 10.2210/pdb4k1c/pdb
• Descriptor: Vacuolar calcium ion transporter, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: structural genomics, psi-biology, protein structure initiative, center for structures of membrane proteins, csmp, membrane protein cax ncx nckx, calcium transport, vacuole, transport protein, membrane protein-metal transport complex, membrane protein/metal transport
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Cellular location: Vacuole membrane; Multi-pass membrane protein: Q99385
• Total number of polymer chains: 2
• Total formula weight: 95310.94

Authors

Waight, A.B.,Pedersen, B.P.,Stroud, R.M.,Center for Structures of Membrane Proteins (CSMP) (deposition date: 2013-04-04, release date: 2013-05-08, Last modification date: 2024-02-28)

Primary citation

Waight, A.B.,Pedersen, B.P.,Schlessinger, A.,Bonomi, M.,Chau, B.H.,Roe-Zurz, Z.,Risenmay, A.J.,Sali, A.,Stroud, R.M.
Structural basis for alternating access of a eukaryotic calcium/proton exchanger.
Nature, 499:107-110, 2013

PubMed 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 Å 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.

PubMed: 23685453
DOI: 10.1038/nature12233

Experimental method

X-RAY DIFFRACTION (2.3 Å)