7y5h: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7y5h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_tropicalis Xenopus tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y5H FirstGlance]. <br> | <table><tr><td colspan='2'>[[7y5h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_tropicalis Xenopus tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y5H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y5H 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]] 3.72Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=7y5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y5h OCA], [https://pdbe.org/7y5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y5h RCSB], [https://www.ebi.ac.uk/pdbsum/7y5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y5h 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=7y5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y5h OCA], [https://pdbe.org/7y5h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y5h RCSB], [https://www.ebi.ac.uk/pdbsum/7y5h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y5h ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ZNT8_XENTR ZNT8_XENTR] | [https://www.uniprot.org/uniprot/ZNT8_XENTR ZNT8_XENTR] Proton-coupled zinc ion antiporter mediating the entry of zinc into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion.[UniProtKB:Q8IWU4] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Zinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet beta cells and is responsible for H(+)-coupled uptake (antiport) of Zn(2+) into the lumen of insulin secretory granules. Structures of human ZnT8 and its prokaryotic homolog YiiP have provided structural basis for constructing a plausible transport cycle for Zn(2+). However, the mechanistic role that protons play in the transport process remains unclear. Here we present a lumen-facing cryo-EM structure of ZnT8 from Xenopus tropicalis (xtZnT8) in the presence of Zn(2+) at a luminal pH (5.5). Compared to a Zn(2+)-bound xtZnT8 structure at a cytosolic pH (7.5), the low-pH structure displays an empty transmembrane Zn(2+)-binding site with a disrupted coordination geometry. Combined with a Zn(2+)-binding assay our data suggest that protons may disrupt Zn(2+) coordination at the transmembrane Zn(2+)-binding site in the lumen-facing state, thus facilitating Zn(2+) release from ZnT8 into the lumen. | Zinc transporter 8 (ZnT8) is mainly expressed in pancreatic islet beta cells and is responsible for H(+)-coupled uptake (antiport) of Zn(2+) into the lumen of insulin secretory granules. Structures of human ZnT8 and its prokaryotic homolog YiiP have provided structural basis for constructing a plausible transport cycle for Zn(2+). However, the mechanistic role that protons play in the transport process remains unclear. Here we present a lumen-facing cryo-EM structure of ZnT8 from Xenopus tropicalis (xtZnT8) in the presence of Zn(2+) at a luminal pH (5.5). Compared to a Zn(2+)-bound xtZnT8 structure at a cytosolic pH (7.5), the low-pH structure displays an empty transmembrane Zn(2+)-binding site with a disrupted coordination geometry. Combined with a Zn(2+)-binding assay our data suggest that protons may disrupt Zn(2+) coordination at the transmembrane Zn(2+)-binding site in the lumen-facing state, thus facilitating Zn(2+) release from ZnT8 into the lumen. | ||
Cryo-EM structure of a eukaryotic zinc transporter at a low pH suggests its Zn(2+)-releasing mechanism.,Zhang S, Fu C, Luo Y, Xie Q, Xu T, Sun Z, Su Z, Zhou X J Struct Biol. | Cryo-EM structure of a eukaryotic zinc transporter at a low pH suggests its Zn(2+)-releasing mechanism.,Zhang S, Fu C, Luo Y, Xie Q, Xu T, Sun Z, Su Z, Zhou X J Struct Biol. 2023 Mar;215(1):107926. doi: 10.1016/j.jsb.2022.107926. Epub 2022 , Dec 1. PMID:36464198<ref>PMID:36464198</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||