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| | <StructureSection load='6xpe' size='340' side='right'caption='[[6xpe]], [[Resolution|resolution]] 4.10Å' scene=''> | | <StructureSection load='6xpe' size='340' side='right'caption='[[6xpe]], [[Resolution|resolution]] 4.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6xpe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XPE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XPE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6xpe]] 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=6XPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XPE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 4.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC30A8, ZNT8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://proteopedia.org/fgij/fg.htm?mol=6xpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xpe OCA], [http://pdbe.org/6xpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xpe RCSB], [http://www.ebi.ac.uk/pdbsum/6xpe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xpe 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=6xpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xpe OCA], [https://pdbe.org/6xpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xpe RCSB], [https://www.ebi.ac.uk/pdbsum/6xpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xpe ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ZNT8_HUMAN ZNT8_HUMAN]] Facilitates the accumulation of zinc from the cytoplasm into intracellular vesicles, being a zinc-efflux transporter. May be a major component for providing zinc to insulin maturation and/or storage processes in insulin-secreting pancreatic beta-cells.<ref>PMID:16984975</ref> | + | [https://www.uniprot.org/uniprot/ZNT8_HUMAN ZNT8_HUMAN] Facilitates the accumulation of zinc from the cytoplasm into intracellular vesicles, being a zinc-efflux transporter. May be a major component for providing zinc to insulin maturation and/or storage processes in insulin-secreting pancreatic beta-cells.<ref>PMID:16984975</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | ZnT8 is a Zn(2+)/H(+) antiporter that belongs to SLC30 family and plays an essential role in regulating Zn(2+) accumulation in the insulin secretory granules of pancreatic beta cells. Dysfunction of ZnT8 is associated with both type 1 and 2 diabetes. However, the Zn(2+)/H(+) exchange mechanism of ZnT8 remains unclear due to the lack of high-resolution structures. Here, we report the cryo-EM structures of human ZnT8 (HsZnT8) in both outward- and inward-facing conformations. HsZnT8 forms a dimeric structure with four Zn(2+) binding sites within each subunit: a highly conserved primary site in transmembrane domain (TMD) housing the Zn(2+) substrate; an interfacial site between TMD and C-terminal domain (CTD) that modulates the Zn(2+) transport activity of HsZnT8; and two adjacent sites buried in the cytosolic domain and chelated by conserved residues from CTD and the His-Cys-His (HCH) motif from the N-terminal segment of the neighboring subunit. A comparison of the outward- and inward-facing structures reveals that the TMD of each HsZnT8 subunit undergoes a large structural rearrangement, allowing for alternating access to the primary Zn(2+) site during the transport cycle. Collectively, our studies provide the structural insights into the Zn(2+)/H(+) exchange mechanism of HsZnT8.
| + | |
| - | | + | |
| - | Cryo-EM structures of human ZnT8 in both outward- and inward-facing conformations.,Xue J, Xie T, Zeng W, Jiang Y, Bai XC Elife. 2020 Jul 29;9. pii: 58823. doi: 10.7554/eLife.58823. PMID:32723473<ref>PMID:32723473</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6xpe" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bai, X C]] | + | [[Category: Bai XC]] |
| - | [[Category: Jiang, Y X]] | + | [[Category: Jiang YX]] |
| - | [[Category: Xue, J]] | + | [[Category: Xue J]] |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Zinc transporter]]
| + | |
| - | [[Category: Znt8]]
| + | |
