8xn1: Difference between revisions
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==Cryo-EM structure of human ZnT3, in the presence of zinc, determined in an inward-facing conformation== | |||
<StructureSection load='8xn1' size='340' side='right'caption='[[8xn1]], [[Resolution|resolution]] 3.14Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8xn1]] 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=8XN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8XN1 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]] 3.14Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1L42:[(2~{S})-3-[[(2~{R})-2,3-bis(oxidanyl)propoxy]-oxidanyl-phosphoryl]oxy-2-hexadecanoyloxy-propyl]+octadecanoate'>A1L42</scene>, <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=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8xn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xn1 OCA], [https://pdbe.org/8xn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xn1 RCSB], [https://www.ebi.ac.uk/pdbsum/8xn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xn1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ZNT3_HUMAN ZNT3_HUMAN] Probable proton-coupled zinc ion antiporter mediating the import of zinc from cytoplasm into synaptic vesicles and participating to cellular zinc ion homeostasis in the brain.<ref>PMID:17349999</ref> <ref>PMID:19521526</ref> <ref>PMID:26647834</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Zinc transporter 1 (ZnT1), the principal carrier of cytosolic zinc to the extracellular milieu, is important for cellular zinc homeostasis and resistance to zinc toxicity. Despite recent advancements in the structural characterization of various zinc transporters, the mechanism by which ZnTs-mediated Zn(2+) translocation is coupled with H(+) or Ca(2+) remains unclear. To visualize the transport dynamics, we determined the cryo-electron microscopy (cryo-EM) structures of human ZnT1 at different functional states. ZnT1 dimerizes via extensive interactions between the cytosolic (CTD), the transmembrane (TMD), and the unique cysteine-rich extracellular (ECD) domains. At pH 7.5, both protomers adopt an outward-facing (OF) conformation, with Zn(2+) ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn(2+) exhibits various conformations [OF/OF, OF/IF (inward-facing), and IF/IF]. These conformational snapshots, together with biochemical investigation and molecular dynamic simulations, shed light on the mechanism underlying the proton-dependence of ZnT1 transport. | |||
Structural insights into human zinc transporter ZnT1 mediated Zn(2+) efflux.,Long Y, Zhu Z, Zhou Z, Yang C, Chao Y, Wang Y, Zhou Q, Wang MW, Qu Q EMBO Rep. 2024 Oct 10. doi: 10.1038/s44319-024-00287-3. PMID:39390258<ref>PMID:39390258</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8xn1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Long Y]] | |||
[[Category: Qu Q]] | |||
[[Category: Zhou Z]] | |||
[[Category: Zhu Z]] | |||
Latest revision as of 10:31, 27 November 2024
Cryo-EM structure of human ZnT3, in the presence of zinc, determined in an inward-facing conformationCryo-EM structure of human ZnT3, in the presence of zinc, determined in an inward-facing conformation
Structural highlights
FunctionZNT3_HUMAN Probable proton-coupled zinc ion antiporter mediating the import of zinc from cytoplasm into synaptic vesicles and participating to cellular zinc ion homeostasis in the brain.[1] [2] [3] Publication Abstract from PubMedZinc transporter 1 (ZnT1), the principal carrier of cytosolic zinc to the extracellular milieu, is important for cellular zinc homeostasis and resistance to zinc toxicity. Despite recent advancements in the structural characterization of various zinc transporters, the mechanism by which ZnTs-mediated Zn(2+) translocation is coupled with H(+) or Ca(2+) remains unclear. To visualize the transport dynamics, we determined the cryo-electron microscopy (cryo-EM) structures of human ZnT1 at different functional states. ZnT1 dimerizes via extensive interactions between the cytosolic (CTD), the transmembrane (TMD), and the unique cysteine-rich extracellular (ECD) domains. At pH 7.5, both protomers adopt an outward-facing (OF) conformation, with Zn(2+) ions coordinated at the TMD binding site by distinct compositions. At pH 6.0, ZnT1 complexed with Zn(2+) exhibits various conformations [OF/OF, OF/IF (inward-facing), and IF/IF]. These conformational snapshots, together with biochemical investigation and molecular dynamic simulations, shed light on the mechanism underlying the proton-dependence of ZnT1 transport. Structural insights into human zinc transporter ZnT1 mediated Zn(2+) efflux.,Long Y, Zhu Z, Zhou Z, Yang C, Chao Y, Wang Y, Zhou Q, Wang MW, Qu Q EMBO Rep. 2024 Oct 10. doi: 10.1038/s44319-024-00287-3. PMID:39390258[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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