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| | <StructureSection load='6u4w' size='340' side='right'caption='[[6u4w]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='6u4w' size='340' side='right'caption='[[6u4w]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6u4w]] is a 1 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=6U4W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6U4W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6u4w]] is a 1 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=6U4W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U4W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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]] 1.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1uow|1uow]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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, SVP65, SYT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6u4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u4w OCA], [https://pdbe.org/6u4w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u4w RCSB], [https://www.ebi.ac.uk/pdbsum/6u4w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u4w ProSAT]</span></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=6u4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u4w OCA], [http://pdbe.org/6u4w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u4w RCSB], [http://www.ebi.ac.uk/pdbsum/6u4w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u4w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SYT1_HUMAN SYT1_HUMAN]] May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. 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. | + | [https://www.uniprot.org/uniprot/SYT1_HUMAN SYT1_HUMAN] May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6u4w" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6u4w" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Synaptotagmin 3D structures|Synaptotagmin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bradberry, M M]] | + | [[Category: Bradberry MM]] |
| - | [[Category: Chapman, E R]] | + | [[Category: Chapman ER]] |
| - | [[Category: Dominguez, M J]] | + | [[Category: Dominguez MJ]] |
| - | [[Category: Sutton, R B]] | + | [[Category: Sutton RB]] |
| - | [[Category: Baker-gordon syndrome]]
| + | |
| - | [[Category: C2 domain]]
| + | |
| - | [[Category: C2b]]
| + | |
| - | [[Category: Exocytosis]]
| + | |
| - | [[Category: Greek key]]
| + | |
| Structural highlights
Function
SYT1_HUMAN May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. 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.
Publication Abstract from PubMed
At neuronal synapses, synaptotagmin-1 (syt1) acts as a Ca(2+) sensor that synchronizes neurotransmitter release with Ca(2+) influx during action potential firing. Heterozygous missense mutations in syt1 have recently been associated with a severe but heterogeneous developmental syndrome, termed syt1-associated neurodevelopmental disorder. Well-defined pathogenic mechanisms, and the basis for phenotypic heterogeneity in this disorder, remain unknown. Here, we report the clinical, physiological, and biophysical characterization of three syt1 mutations from human patients. Synaptic transmission was impaired in neurons expressing mutant variants, which demonstrated potent, graded dominant-negative effects. Biophysical interrogation of the mutant variants revealed novel mechanistic features concerning the cooperative action, and functional specialization, of the tandem Ca(2+)-sensing domains of syt1. These mechanistic studies led to the discovery that a clinically approved K(+) channel antagonist is able to rescue the dominant-negative heterozygous phenotype. Our results establish a molecular cause, basis for phenotypic heterogeneity, and potential treatment approach for syt1-associated neurodevelopmental disorder.
Molecular Basis for Synaptotagmin-1-Associated Neurodevelopmental Disorder.,Bradberry MM, Courtney NA, Dominguez MJ, Lofquist SM, Knox AT, Sutton RB, Chapman ER Neuron. 2020 Apr 21. pii: S0896-6273(20)30272-5. doi:, 10.1016/j.neuron.2020.04.003. PMID:32362337[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bradberry MM, Courtney NA, Dominguez MJ, Lofquist SM, Knox AT, Sutton RB, Chapman ER. Molecular Basis for Synaptotagmin-1-Associated Neurodevelopmental Disorder. Neuron. 2020 Apr 21. pii: S0896-6273(20)30272-5. doi:, 10.1016/j.neuron.2020.04.003. PMID:32362337 doi:http://dx.doi.org/10.1016/j.neuron.2020.04.003
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