2cjs

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[[Image:2cjs.gif|left|200px]]<br />
 
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<applet load="2cjs" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2cjs, resolution 1.78&Aring;" />
 
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'''STRUCTURAL BASIS FOR A MUNC13-1 HOMODIMER- MUNC13-1- RIM HETERODIMER SWITCH: C2-DOMAINS AS VERSATILE PROTEIN-PROTEIN INTERACTION MODULES'''<br />
 
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==Overview==
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==Structural Basis for a Munc13-1 Homodimer - Munc13-1 - RIM Heterodimer Switch: C2-domains as Versatile Protein-Protein Interaction Modules==
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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.
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<StructureSection load='2cjs' size='340' side='right'caption='[[2cjs]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2cjs]] is a 3 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=2CJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CJS FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78&#8491;</td></tr>
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<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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cjs OCA], [https://pdbe.org/2cjs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cjs RCSB], [https://www.ebi.ac.uk/pdbsum/2cjs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cjs ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cj/2cjs_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cjs ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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>
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2CJS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ZN, EDO and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CJS OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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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 Jun;4(7):e192. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16732694 16732694]
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</div>
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[[Category: Protein complex]]
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<div class="pdbe-citations 2cjs" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Dai, H.]]
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[[Category: Dai H]]
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[[Category: Dulubova, I.]]
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[[Category: Dulubova I]]
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[[Category: Lu, J.]]
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[[Category: Lu J]]
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[[Category: Machius, M.]]
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[[Category: Machius M]]
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[[Category: Rizo, J.]]
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[[Category: Rizo J]]
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[[Category: Sudhof, T.C.]]
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[[Category: Sudhof TC]]
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[[Category: Tomchick, D.R.]]
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[[Category: Tomchick DR]]
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[[Category: EDO]]
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[[Category: GOL]]
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[[Category: ZN]]
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[[Category: alternative splicing]]
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[[Category: c2 domains]]
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[[Category: coiled coil]]
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[[Category: exocytosis]]
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[[Category: metal-binding]]
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[[Category: munc13]]
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[[Category: neurotransmitter release]]
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[[Category: neurotransmitter transport]]
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[[Category: phorbol-ester binding]]
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[[Category: protein-protein interactions]]
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[[Category: rim]]
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[[Category: synapse]]
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[[Category: synaptosome]]
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[[Category: transport]]
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[[Category: zinc]]
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[[Category: zinc finger]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:56:19 2007''
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Current revision

Structural Basis for a Munc13-1 Homodimer - Munc13-1 - RIM Heterodimer Switch: C2-domains as Versatile Protein-Protein Interaction Modules

PDB ID 2cjs

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