View source for 2cjt


==Structural Basis for a Munc13-1 Homodimer - Munc13-1 - RIM Heterodimer Switch: C2-domains as Versatile Protein-Protein Interaction Modules==
<StructureSection load='2cjt' size='340' side='right'caption='[[2cjt]], [[Resolution|resolution]] 1.44&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2cjt]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CJT 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]] 1.44&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=2cjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cjt OCA], [https://pdbe.org/2cjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cjt RCSB], [https://www.ebi.ac.uk/pdbsum/2cjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cjt 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 ==
C(2) domains are well characterized as Ca(2+)/phospholipid-binding modules, but little is known about how they mediate protein-protein interactions. In neurons, a Munc13-1 C(2)A-domain/RIM zinc-finger domain (ZF) heterodimer couples synaptic vesicle priming to presynaptic plasticity. We now show that the Munc13-1 C(2)A domain homodimerizes, and that homodimerization competes with Munc13-1/RIM heterodimerization. X-ray diffraction studies guided by nuclear magnetic resonance (NMR) experiments reveal the crystal structures of the Munc13-1 C(2)A-domain homodimer and the Munc13-1 C(2)A-domain/RIM ZF heterodimer at 1.44 A and 1.78 A resolution, respectively. The C(2)A domain adopts a beta-sandwich structure with a four-stranded concave side that mediates homodimerization, leading to the formation of an eight-stranded beta-barrel. In contrast, heterodimerization involves the bottom tip of the C(2)A-domain beta-sandwich and a C-terminal alpha-helical extension, which wrap around the RIM ZF domain. Our results describe the structural basis for a Munc13-1 homodimer-Munc13-1/RIM heterodimer switch that may be crucial for vesicle priming and presynaptic plasticity, uncovering at the same time an unexpected versatility of C(2) domains as protein-protein interaction modules, and illustrating the power of combining NMR spectroscopy and X-ray crystallography to study protein complexes.

Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch.,Lu J, Machius M, Dulubova I, Dai H, Sudhof TC, Tomchick DR, Rizo J PLoS Biol. 2006 Jul;4(7):e192. PMID:16732694<ref>PMID:16732694</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2cjt" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Dai H]]
[[Category: Dulubova I]]
[[Category: Lu J]]
[[Category: Machius M]]
[[Category: Rizo J]]
[[Category: Sudhof TC]]
[[Category: Tomchick DR]]