5vfe

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<StructureSection load='5vfe' size='340' side='right' caption='[[5vfe]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
<StructureSection load='5vfe' size='340' side='right' caption='[[5vfe]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5vfe]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VFE FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5vfe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VFE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PB:LEAD+(II)+ION'>PB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PB:LEAD+(II)+ION'>PB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vff|5vff]], [[5vfg|5vfg]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vff|5vff]], [[5vfg|5vfg]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Syt1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=5vfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vfe OCA], [http://pdbe.org/5vfe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vfe RCSB], [http://www.ebi.ac.uk/pdbsum/5vfe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vfe ProSAT]</span></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=5vfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vfe OCA], [http://pdbe.org/5vfe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vfe RCSB], [http://www.ebi.ac.uk/pdbsum/5vfe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vfe ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SYT1_MOUSE SYT1_MOUSE]] May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (PubMed:7961887). It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes (By similarity).[UniProtKB:P21579]<ref>PMID:7961887</ref>
[[http://www.uniprot.org/uniprot/SYT1_MOUSE SYT1_MOUSE]] May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (PubMed:7961887). It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes (By similarity).[UniProtKB:P21579]<ref>PMID:7961887</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Lead (Pb) is a potent neurotoxin that disrupts synaptic neurotransmission. We report that Synaptotagmin I (SytI), a key regulator of Ca2+-evoked neurotransmitter release, has two high-affinity Pb2+ binding sites that belong to its cytosolic C2A and C2B domains. The crystal structures of Pb2+-complexed C2 domains revealed that protein-bound Pb2+ ions have holodirected coordination geometries and all-oxygen coordination spheres. The on-rate constants of Pb2+ binding to the C2 domains of SytI are comparable to those of Ca2+ and are diffusion-limited. In contrast, the off-rate constants are at least two orders of magnitude smaller, indicating that Pb2+ can serve as both a thermodynamic and kinetic trap for the C2 domains. We demonstrate, using NMR spectroscopy, that population of these sites by Pb2+ ions inhibits further Ca2+ binding despite the existing coordination vacancies. Our work offers a unique insight into the bioinorganic chemistry of Pb(ii) and suggests a mechanism by which low concentrations of Pb2+ ions can interfere with the Ca2+-dependent function of SytI in the cell.
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High affinity interactions of Pb(2+) with synaptotagmin I.,Katti S, Her B, Srivastava AK, Taylor AB, Lockless SW, Igumenova TI Metallomics. 2018 Sep 19;10(9):1211-1222. doi: 10.1039/c8mt00135a. PMID:30063057<ref>PMID:30063057</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 5vfe" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Synaptotagmin|Synaptotagmin]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Lk3 transgenic mice]]
[[Category: Hart, P J]]
[[Category: Hart, P J]]
[[Category: Igumenova, T I]]
[[Category: Igumenova, T I]]

Revision as of 08:43, 19 December 2018

Synaptotagmin 1 C2A domain, lead-bound

5vfe, resolution 1.38Å

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