View source for 6nyc


==Munc13-1 C2B-domain, calcium free==
<StructureSection load='6nyc' size='340' side='right'caption='[[6nyc]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nyc]] 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=3kwt 3kwt]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NYC 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]] 1.893&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B3P:2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>B3P</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6nyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nyc OCA], [https://pdbe.org/6nyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nyc RCSB], [https://www.ebi.ac.uk/pdbsum/6nyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nyc 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> 
<div style="background-color:#fffaf0;">
== 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>
</div>
<div class="pdbe-citations 6nyc" 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]]