7tx9: Difference between revisions
New page: '''Unreleased structure''' The entry 7tx9 is ON HOLD until Paper Publication Authors: Dominguez, M.J., Karmakar, S., Fuson, K.L., Sutton, R.B. Description: Human Synaptotagmin-1 C2B Y3... |
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==Human Synaptotagmin-1 C2B Y312F Ca2+ bound== | |||
<StructureSection load='7tx9' size='340' side='right'caption='[[7tx9]], [[Resolution|resolution]] 1.34Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7tx9]] 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=7TX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TX9 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]] 1.34Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PG:2-(2-{2-[2-(2-METHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHANOL'>1PG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=7tx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tx9 OCA], [https://pdbe.org/7tx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tx9 RCSB], [https://www.ebi.ac.uk/pdbsum/7tx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tx9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/J3KQA0_HUMAN J3KQA0_HUMAN] Calcium sensor that participates in triggering neurotransmitter release at the synapse. 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. Plays a role in dendrite formation by melanocytes.[ARBA:ARBA00045706] 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.[RuleBase:RU367154] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Synaptotagmin-1 (syt1) functions as the Ca(2+)-dependent sensor that triggers the rapid and synchronous release of neurotransmitters from neurotransmitter-containing vesicles during neuronal exocytosis. The syt1 protein has two homologous tandem C2 domains that interact with phospholipids in a Ca(2+)-dependent manner. Despite the crucial role of syt1 in exocytosis, the precise interactions between Ca(2+), syt1, and phospholipids are not fully understood. In a study involving recessive lethal mutations in the syt1 gene, a specific mutation named AD3 was generated in Drosophila syt1, resulting in a significant reduction in Ca(2+)-dependent exocytosis. Further investigation revealed that the AD3 mutation was a missense mutation located in a conserved consensus sequence within the C2B domain of Drosophila syt1. However, the biophysical impact of the AD3 mutation had not been analyzed. Our study uses x-ray crystallography, isothermal titration calorimetry, thermodynamic analysis, and molecular dynamics simulation to show that the primary defect caused by the AD3 mutation in the syt1 protein is reduced thermodynamic stability. This instability alters the population of Ca(2+)-receptive states, leading to two major consequences: decreased affinity for calcium ions and compromised stabilization of the domain normally enhanced by Ca(2+). We conclude that this conserved residue acts as a structural constraint, delimiting the movement of loop 3 within the pocket and ultimately influencing the affinity of the calcium ion binding with the C2 domain. | |||
The AD3 locus of synaptotagmin-1 C2 domains modulates domain stability.,Dominguez MJ, Bui AA, Villarreal J, Snow A, Karmakar S, Harsini FM, Rock PJ, Rice AM, Fuson KL, Sutton RB Biophys J. 2024 Nov 22:S0006-3495(24)00718-5. doi: 10.1016/j.bpj.2024.11.009. PMID:39578407<ref>PMID:39578407</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7tx9" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Karmakar | ==See Also== | ||
[[Category: | *[[Synaptotagmin 3D structures|Synaptotagmin 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Dominguez MJ]] | |||
[[Category: Fuson KL]] | |||
[[Category: Karmakar S]] | |||
[[Category: Sutton RB]] | |||