|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Synaptotagmin 1 C2A domain, lead-bound== | | ==Synaptotagmin 1 C2A domain, lead-bound== |
| - | <StructureSection load='5vfe' size='340' side='right' caption='[[5vfe]], [[Resolution|resolution]] 1.38Å' scene=''> | + | <StructureSection load='5vfe' size='340' side='right'caption='[[5vfe]], [[Resolution|resolution]] 1.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <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> | + | <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='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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.38Å</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='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='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'>[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> |
| - | <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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 21: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Synaptotagmin|Synaptotagmin]] | + | *[[Synaptotagmin 3D structures|Synaptotagmin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Hart, P J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Igumenova, T I]] | + | [[Category: Hart PJ]] |
| - | [[Category: Taylor, A B]] | + | [[Category: Igumenova TI]] |
| - | [[Category: C2a domain]] | + | [[Category: Taylor AB]] |
| - | [[Category: Metal binding protein]]
| + | |
| Structural highlights
Function
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][1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fukuda M, Aruga J, Niinobe M, Aimoto S, Mikoshiba K. Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II. J Biol Chem. 1994 Nov 18;269(46):29206-11. PMID:7961887
- ↑ Katti S, Her B, Srivastava AK, Taylor AB, Lockless SW, Igumenova TI. High affinity interactions of Pb(2+) with synaptotagmin I. Metallomics. 2018 Sep 19;10(9):1211-1222. doi: 10.1039/c8mt00135a. PMID:30063057 doi:http://dx.doi.org/10.1039/c8mt00135a
|
