|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4p5w' size='340' side='right'caption='[[4p5w]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='4p5w' size='340' side='right'caption='[[4p5w]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4p5w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P5W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4p5w]] is a 2 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=4P5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P5W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </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></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5w OCA], [http://pdbe.org/4p5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4p5w RCSB], [http://www.ebi.ac.uk/pdbsum/4p5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5w ProSAT]</span></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=4p5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p5w OCA], [https://pdbe.org/4p5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p5w RCSB], [https://www.ebi.ac.uk/pdbsum/4p5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p5w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CMC2_HUMAN CMC2_HUMAN]] Citrullinemia type II;Neonatal intrahepatic cholestasis due to citrin deficiency. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/S2513_HUMAN S2513_HUMAN] Citrullinemia type II;Neonatal intrahepatic cholestasis due to citrin deficiency. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CMC2_HUMAN CMC2_HUMAN]] Catalyzes the calcium-dependent exchange of cytoplasmic glutamate with mitochondrial aspartate across the mitochondrial inner membrane. May have a function in the urea cycle.<ref>PMID:11566871</ref> | + | [https://www.uniprot.org/uniprot/S2513_HUMAN S2513_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). 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 24: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kunji, E R.S]] | + | [[Category: Kunji ERS]] |
| - | [[Category: Ruprecht, J J]] | + | [[Category: Ruprecht JJ]] |
| - | [[Category: Thangaratnarajah, C]] | + | [[Category: Thangaratnarajah C]] |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Disease
S2513_HUMAN Citrullinemia type II;Neonatal intrahepatic cholestasis due to citrin deficiency. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.
Function
S2513_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). 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).[1]
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Palmieri L, Pardo B, Lasorsa FM, del Arco A, Kobayashi K, Iijima M, Runswick MJ, Walker JE, Saheki T, Satrustegui J, Palmieri F. Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 2001 Sep 17;20(18):5060-9. PMID:11566871 doi:http://dx.doi.org/10.1093/emboj/20.18.5060
- ↑ Thangaratnarajah C, Ruprecht JJ, Kunji ER. Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. Nat Commun. 2014 Nov 20;5:5491. doi: 10.1038/ncomms6491. PMID:25410934 doi:http://dx.doi.org/10.1038/ncomms6491
|
