4p5x
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==Structure of the N-terminal domain of the human mitochondrial aspartate/glutamate carrier Aralar in the calcium-bound state== | ==Structure of the N-terminal domain of the human mitochondrial aspartate/glutamate carrier Aralar in the calcium-bound state== | ||
| - | <StructureSection load='4p5x' size='340' side='right' caption='[[4p5x]], [[Resolution|resolution]] 2.26Å' scene=''> | + | <StructureSection load='4p5x' size='340' side='right'caption='[[4p5x]], [[Resolution|resolution]] 2.26Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4p5x]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P5X OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4p5x]] is a 1 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=4P5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P5X FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.261Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4p5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5x OCA], [https://pdbe.org/4p5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p5x RCSB], [https://www.ebi.ac.uk/pdbsum/4p5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5x ProSAT]</span></td></tr> |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/S2512_HUMAN S2512_HUMAN] Epileptic encephalopathy with global cerebral demyelination. The disease is caused by variants affecting the gene represented in this entry. |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/S2512_HUMAN S2512_HUMAN] Mitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle (PubMed:11566871, PubMed:19641205, PubMed:24515575). Also mediates the uptake of L-cysteinesulfinate by mitochondria in exchange of L-glutamate and proton. Can also exchange L-cysteinesulfinate with aspartate in their anionic form without any proton translocation (PubMed:11566871).<ref>PMID:11566871</ref> <ref>PMID:19641205</ref> <ref>PMID:24515575</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The transport activity of human mitochondrial aspartate/glutamate carriers is central to the malate-aspartate shuttle, urea cycle, gluconeogenesis and myelin synthesis. They have a unique three-domain structure, comprising a calcium-regulated N-terminal domain with eight EF-hands, a mitochondrial carrier domain, and a C-terminal domain. Here we present the calcium-bound and calcium-free structures of the N- and C-terminal domains, elucidating the mechanism of calcium regulation. Unexpectedly, EF-hands 4-8 are involved in dimerization of the carrier and form a static unit, whereas EF-hands 1-3 form a calcium-responsive mobile unit. On calcium binding, an amphipathic helix of the C-terminal domain binds to the N-terminal domain, opening a vestibule. In the absence of calcium, the mobile unit closes the vestibule. Opening and closing of the vestibule might regulate access of substrates to the carrier domain, which is involved in their transport. These structures provide a framework for understanding cases of the mitochondrial disease citrin deficiency. | ||
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| + | Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers.,Thangaratnarajah C, Ruprecht JJ, Kunji ER Nat Commun. 2014 Nov 20;5:5491. doi: 10.1038/ncomms6491. PMID:25410934<ref>PMID:25410934</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4p5x" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Kunji ERS]] |
| - | [[Category: | + | [[Category: Ruprecht JJ]] |
| - | [[Category: | + | [[Category: Thangaratnarajah C]] |
| - | + | ||
| - | + | ||
Current revision
Structure of the N-terminal domain of the human mitochondrial aspartate/glutamate carrier Aralar in the calcium-bound state
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