Publication Date:
2013-05-21
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702627/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702627/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waight, Andrew B -- Pedersen, Bjorn Panyella -- Schlessinger, Avner -- Bonomi, Massimiliano -- Chau, Bryant H -- Roe-Zurz, Zygy -- Risenmay, Aaron J -- Sali, Andrej -- Stroud, Robert M -- GM073210/GM/NIGMS NIH HHS/ -- GM24485/GM/NIGMS NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- R01 GM024485/GM/NIGMS NIH HHS/ -- R37 GM024485/GM/NIGMS NIH HHS/ -- T32 GM008284/GM/NIGMS NIH HHS/ -- U01 GM061390/GM/NIGMS NIH HHS/ -- U01 GM61390/GM/NIGMS NIH HHS/ -- U19 GM061390/GM/NIGMS NIH HHS/ -- U54 GM094625/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Jul 4;499(7456):107-10. doi: 10.1038/nature12233. Epub 2013 May 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23685453" target="_blank"〉PubMed〈/a〉
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
;
*Protons
;
Saccharomyces cerevisiae/*chemistry
;
Saccharomyces cerevisiae Proteins/*chemistry/*metabolism
;
Structure-Activity Relationship
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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