This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4p60

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Structure of the N-terminal domain of the human mitochondrial aspartate/glutamate carrier Aralar in the apo state

Structural highlights

4p60 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

S2512_HUMAN Epileptic encephalopathy with global cerebral demyelination. The disease is caused by variants affecting the gene represented in this entry.

Function

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).^[1] ^[2] ^[3]

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^[4]

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
↑ Wibom R, Lasorsa FM, Tohonen V, Barbaro M, Sterky FH, Kucinski T, Naess K, Jonsson M, Pierri CL, Palmieri F, Wedell A. AGC1 deficiency associated with global cerebral hypomyelination. N Engl J Med. 2009 Jul 30;361(5):489-95. doi: 10.1056/NEJMoa0900591. PMID:19641205 doi:http://dx.doi.org/10.1056/NEJMoa0900591
↑ Falk MJ, Li D, Gai X, McCormick E, Place E, Lasorsa FM, Otieno FG, Hou C, Kim CE, Abdel-Magid N, Vazquez L, Mentch FD, Chiavacci R, Liang J, Liu X, Jiang H, Giannuzzi G, Marsh ED, Yiran G, Tian L, Palmieri F, Hakonarson H. AGC1 Deficiency Causes Infantile Epilepsy, Abnormal Myelination, and Reduced N-Acetylaspartate. JIMD Rep. 2014;14:77-85. doi: 10.1007/8904_2013_287. Epub 2014 Feb 11. PMID:24515575 doi:http://dx.doi.org/10.1007/8904_2013_287
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4p60"

Categories: Homo sapiens | Large Structures | Kunji ERS | Ruprecht JJ | Thangaratnarajah C

@@ Line 1: / Line 1: @@
 ==Structure of the N-terminal domain of the human mitochondrial aspartate/glutamate carrier Aralar in the apo state==
-<StructureSection load='4p60' size='340' side='right' caption='[[4p60]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='4p60' size='340' side='right'caption='[[4p60]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4p60]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P60 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P60 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4p60]] 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=4P60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P60 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4p5x|4p5x]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=4p60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p60 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p60 RCSB], [http://www.ebi.ac.uk/pdbsum/4p60 PDBsum]</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=4p60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p60 OCA], [https://pdbe.org/4p60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p60 RCSB], [https://www.ebi.ac.uk/pdbsum/4p60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p60 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/CMC1_HUMAN CMC1_HUMAN]] Epileptic encephalopathy with global cerebral demyelination. The disease is caused by mutations affecting the gene represented in this entry.
+[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 ==
-[[http://www.uniprot.org/uniprot/CMC1_HUMAN CMC1_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/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 ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4p60" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Kunji, E R.S]]
+[[Category: Homo sapiens]]
-[[Category: Ruprecht, J J]]
+[[Category: Large Structures]]
-[[Category: Thangaratnarajah, C]]
+[[Category: Kunji ERS]]
-[[Category: Transport protein]]
+[[Category: Ruprecht JJ]]
+[[Category: Thangaratnarajah C]]

4p60

From Proteopedia

Current revision

Structure of the N-terminal domain of the human mitochondrial aspartate/glutamate carrier Aralar in the apo state

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox