View source for 4zcv


==Structure of calcium-bound regulatory domain of the human ATP-Mg/Pi carrier in the P212121 form==
<StructureSection load='4zcv' size='340' side='right'caption='[[4zcv]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zcv]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZCV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zcv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zcv OCA], [https://pdbe.org/4zcv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zcv RCSB], [https://www.ebi.ac.uk/pdbsum/4zcv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zcv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SCMC1_HUMAN SCMC1_HUMAN] Calcium-dependent mitochondrial solute carrier. Mitochondrial solute carriers shuttle metabolites, nucleotides, and cofactors through the mitochondrial inner membrane. May act as a ATP-Mg/Pi exchanger that mediates the transport of Mg-ATP in exchange for phosphate, catalyzing the net uptake or efflux of adenine nucleotides into or from the mitochondria.<ref>PMID:15123600</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The mitochondrial ATP-Mg/Pi carrier imports adenine nucleotides from the cytosol into the mitochondrial matrix and exports phosphate. The carrier is regulated by the concentration of cytosolic calcium, altering the size of the adenine nucleotide pool in the mitochondrial matrix in response to energetic demands. The protein consists of three domains; (i) the N-terminal regulatory domain, which is formed of two pairs of fused calcium-binding EF-hands, (ii) the C-terminal mitochondrial carrier domain, which is involved in transport, and (iii) a linker region with an amphipathic alpha-helix of unknown function. The mechanism by which calcium binding to the regulatory domain modulates substrate transport in the carrier domain has not been resolved. Here, we present two new crystal structures of the regulatory domain of the human isoform 1. Careful analysis by SEC confirmed that although the regulatory domain crystallised as dimers, full-length ATP-Mg/Pi carrier is monomeric. Therefore, the ATP-Mg/Pi carrier must have a different mechanism of calcium regulation than the architecturally related aspartate/glutamate carrier, which is dimeric. The structure showed that an amphipathic alpha-helix is bound to the regulatory domain in a hydrophobic cleft of EF-hand 3/4. Detailed bioinformatics analyses of different EF-hand states indicate that upon release of calcium, EF-hands close, meaning that the regulatory domain would release the amphipathic alpha-helix. We propose a mechanism for ATP-Mg/Pi carriers in which the amphipathic alpha-helix becomes mobile upon release of calcium and could block the transport of substrates across the mitochondrial inner membrane.

Calcium-induced conformational changes in the regulatory domain of the human mitochondrial ATP-Mg/Pi carrier.,Harborne SP, Ruprecht JJ, Kunji ER Biochim Biophys Acta. 2015 Jul 9;1847(10):1245-1253. doi:, 10.1016/j.bbabio.2015.07.002. PMID:26164100<ref>PMID:26164100</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zcv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Harborne SPD]]
[[Category: Kunji ERS]]
[[Category: Ruprecht JJ]]