View source for 5vfe


==Synaptotagmin 1 C2A domain, lead-bound==
<StructureSection load='5vfe' size='340' side='right'caption='[[5vfe]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vfe]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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 [https://proteopedia.org/fgij/fg.htm?mol=5VFE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PB:LEAD+(II)+ION'>PB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5vfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vfe OCA], [https://pdbe.org/5vfe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vfe RCSB], [https://www.ebi.ac.uk/pdbsum/5vfe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vfe ProSAT]</span></td></tr>
</table>
== Function ==
[https://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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== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5vfe" style="background-color:#fffaf0;"></div>

==See Also==
*[[Synaptotagmin 3D structures|Synaptotagmin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Hart PJ]]
[[Category: Igumenova TI]]
[[Category: Taylor AB]]