View source for 6nyt


==Munc13-1 C2B-domain, calcium bound==
<StructureSection load='6nyt' size='340' side='right'caption='[[6nyt]], [[Resolution|resolution]] 1.37&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nyt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3kwu 3kwu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NYT 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]] 1.369&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6nyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nyt OCA], [https://pdbe.org/6nyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nyt RCSB], [https://www.ebi.ac.uk/pdbsum/6nyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nyt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UN13A_RAT UN13A_RAT] Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. Also involved in secretory granule priming in insulin secretion.<ref>PMID:9697857</ref> <ref>PMID:11343654</ref> <ref>PMID:11792326</ref> 
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== Publication Abstract from PubMed ==
Munc13 is a multidomain protein present in presynaptic active zones that mediates the priming and plasticity of synaptic vesicle exocytosis, but the mechanisms involved remain unclear. Here we use biophysical, biochemical and electrophysiological approaches to show that the central C(2)B domain of Munc13 functions as a Ca(2+) regulator of short-term synaptic plasticity. The crystal structure of the C(2)B domain revealed an unusual Ca(2+)-binding site with an amphipathic alpha-helix. This configuration confers onto the C(2)B domain unique Ca(2+)-dependent phospholipid-binding properties that favor phosphatidylinositolphosphates. A mutation that inactivated Ca(2+)-dependent phospholipid binding to the C(2)B domain did not alter neurotransmitter release evoked by isolated action potentials, but it did depress release evoked by action-potential trains. In contrast, a mutation that increased Ca(2+)-dependent phosphatidylinositolbisphosphate binding to the C(2)B domain enhanced release evoked by isolated action potentials and by action-potential trains. Our data suggest that, during repeated action potentials, Ca(2+) and phosphatidylinositolphosphate binding to the Munc13 C(2)B domain potentiate synaptic vesicle exocytosis, thereby offsetting synaptic depression induced by vesicle depletion.

Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis.,Shin OH, Lu J, Rhee JS, Tomchick DR, Pang ZP, Wojcik SM, Camacho-Perez M, Brose N, Machius M, Rizo J, Rosenmund C, Sudhof TC Nat Struct Mol Biol. 2010 Mar;17(3):280-8. Epub 2010 Feb 14. PMID:20154707<ref>PMID:20154707</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 6nyt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Lu J]]
[[Category: Machius M]]
[[Category: Rizo J]]
[[Category: Tomchick DR]]