8j74

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Current revision (14:42, 6 November 2024) (edit) (undo)
 
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<table><tr><td colspan='2'>[[8j74]] 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=8J74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8J74 FirstGlance]. <br>
<table><tr><td colspan='2'>[[8j74]] 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=8J74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8J74 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AV0:Lauryl+Maltose+Neopentyl+Glycol'>AV0</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=HC6:(2S,2S)-2,2-BIPHENYL-4,4-DIYLBIS(2-HYDROXY-4,4-DIMETHYLMORPHOLIN-4-IUM)'>HC6</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=R16:HEXADECANE'>R16</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AV0:2-decyl-2-{[(4-O-alpha-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]methyl}dodecyl+4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside'>AV0</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=HC6:(2S,2S)-2,2-BIPHENYL-4,4-DIYLBIS(2-HYDROXY-4,4-DIMETHYLMORPHOLIN-4-IUM)'>HC6</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=R16:HEXADECANE'>R16</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8j74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8j74 OCA], [https://pdbe.org/8j74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8j74 RCSB], [https://www.ebi.ac.uk/pdbsum/8j74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8j74 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=8j74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8j74 OCA], [https://pdbe.org/8j74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8j74 RCSB], [https://www.ebi.ac.uk/pdbsum/8j74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8j74 ProSAT]</span></td></tr>
</table>
</table>
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[https://www.uniprot.org/uniprot/SC5A7_HUMAN SC5A7_HUMAN] Distal hereditary motor neuropathy type 7;Presynaptic congenital myasthenic syndromes. 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.
[https://www.uniprot.org/uniprot/SC5A7_HUMAN SC5A7_HUMAN] Distal hereditary motor neuropathy type 7;Presynaptic congenital myasthenic syndromes. 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 ==
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[https://www.uniprot.org/uniprot/SC5A7_HUMAN SC5A7_HUMAN] High-affinity Na(+)-coupled choline transmembrane symporter (PubMed:11027560, PubMed:11068039, PubMed:12969261, PubMed:17005849, PubMed:23141292, PubMed:23132865, PubMed:12237312, PubMed:27569547). Functions as an electrogenic, voltage-dependent transporter with variable charge/choline stoichiometry (PubMed:17005849). Choline uptake and choline-induced current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion rather than cotransported ion (PubMed:11068039, PubMed:17005849, PubMed:12237312). Plays a critical role in acetylcholine (ACh) synthesis by taking up the substrate choline from the synaptic cleft into the presynaptic nerve terminals after neurotransmitter release (PubMed:27569547). SLC5A7/CHT1-mediated choline high-affinity transport in cholinergic neurons is the rate-limiting step for production of ACh, thereby facilitating communication by subsequent action potentials (PubMed:11027560). Localized predominantly in presynaptic terminal intracellular organelles, and translocated to the plasma membrane in active form in response to neuronal activity (PubMed:12969261, PubMed:15953352).<ref>PMID:11027560</ref> <ref>PMID:11068039</ref> <ref>PMID:12237312</ref> <ref>PMID:12969261</ref> <ref>PMID:15953352</ref> <ref>PMID:17005849</ref> <ref>PMID:23132865</ref> <ref>PMID:23141292</ref> <ref>PMID:27569547</ref>
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[https://www.uniprot.org/uniprot/SC5A7_HUMAN SC5A7_HUMAN] High-affinity Na(+)-coupled choline transmembrane symporter (PubMed:11027560, PubMed:11068039, PubMed:12237312, PubMed:12969261, PubMed:17005849, PubMed:23132865, PubMed:23141292, PubMed:27569547). Functions as an electrogenic, voltage-dependent transporter with variable charge/choline stoichiometry (PubMed:17005849). Choline uptake and choline-induced current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion rather than cotransported ion (PubMed:11068039, PubMed:12237312, PubMed:17005849). Plays a critical role in acetylcholine (ACh) synthesis by taking up the substrate choline from the synaptic cleft into the presynaptic nerve terminals after neurotransmitter release (PubMed:27569547). SLC5A7/CHT1-mediated choline high-affinity transport in cholinergic neurons is the rate-limiting step for production of ACh, thereby facilitating communication by subsequent action potentials (PubMed:11027560). Localized predominantly in presynaptic terminal intracellular organelles, and translocated to the plasma membrane in active form in response to neuronal activity (PubMed:12969261, PubMed:15953352).<ref>PMID:11027560</ref> <ref>PMID:11068039</ref> <ref>PMID:12237312</ref> <ref>PMID:12969261</ref> <ref>PMID:15953352</ref> <ref>PMID:17005849</ref> <ref>PMID:23132865</ref> <ref>PMID:23141292</ref> <ref>PMID:27569547</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Choline is a vital nutrient and a precursor for the biosynthesis of essential metabolites, including acetylcholine (ACh), that play a central role in fetal development, especially in the brain. In cholinergic neurons, the high-affinity choline transporter (CHT1) provides an extraordinarily efficient reuptake mechanism to reutilize choline derived from intrasynaptical ACh hydrolysis and maintain ACh synthesis in the presynapse. Here, we determined structures of human CHT1 in three discrete states: the outward-facing state bound with the competitive inhibitor hemicholinium-3 (HC-3); the inward-facing occluded state bound with the substrate choline; and the inward-facing apo open state. Our structures and functional characterizations elucidate how the inhibitor and substrate are recognized. Moreover, our findings shed light on conformational changes when transitioning from an outward-facing to an inward-facing state and establish a framework for understanding the transport cycle, which relies on the stabilization of the outward-facing state by a short intracellular helix, IH1.
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Transport mechanism of presynaptic high-affinity choline uptake by CHT1.,Qiu Y, Gao Y, Huang B, Bai Q, Zhao Y Nat Struct Mol Biol. 2024 Apr;31(4):701-709. doi: 10.1038/s41594-024-01259-w. , Epub 2024 Apr 8. PMID:38589607<ref>PMID:38589607</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8j74" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Current revision

Human high-affinity choline transporter CHT1 in the HC-3-bound outward-facing open conformation, dimeric state

PDB ID 8j74

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