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| | ==Structural basis of the Munc13-1/Ca2+-Calmodulin interaction: A novel 1-26 calmodulin binding motif with a bipartite binding mode== | | ==Structural basis of the Munc13-1/Ca2+-Calmodulin interaction: A novel 1-26 calmodulin binding motif with a bipartite binding mode== |
| - | <StructureSection load='2kdu' size='340' side='right'caption='[[2kdu]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kdu' size='340' side='right'caption='[[2kdu]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kdu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KDU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kdu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KDU FirstGlance]. <br> |
| - | </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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">calm1, calm2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</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></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=2kdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kdu OCA], [https://pdbe.org/2kdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kdu RCSB], [https://www.ebi.ac.uk/pdbsum/2kdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kdu ProSAT]</span></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=2kdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kdu OCA], [https://pdbe.org/2kdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kdu RCSB], [https://www.ebi.ac.uk/pdbsum/2kdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kdu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CALM_XENLA CALM_XENLA]] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. [[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>
| + | [https://www.uniprot.org/uniprot/CALM1_XENLA CALM1_XENLA] Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: African clawed frog]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Becker, S]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Brose, N]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Carlomagno, T]] | + | [[Category: Becker S]] |
| - | [[Category: Coudevylle, N]] | + | [[Category: Brose N]] |
| - | [[Category: Dimova, K]] | + | [[Category: Carlomagno T]] |
| - | [[Category: Griesinger, C]] | + | [[Category: Coudevylle N]] |
| - | [[Category: Jahn, O]] | + | [[Category: Dimova K]] |
| - | [[Category: Junge, H]] | + | [[Category: Griesinger C]] |
| - | [[Category: Maestre-Martinez, M]] | + | [[Category: Jahn O]] |
| - | [[Category: Rodriguez-Castaneda, F A]] | + | [[Category: Junge H]] |
| - | [[Category: Acetylation]]
| + | [[Category: Maestre-Martinez M]] |
| - | [[Category: Alternative splicing]]
| + | [[Category: Rodriguez-Castaneda FA]] |
| - | [[Category: Calcium]]
| + | |
| - | [[Category: Calmodulin]]
| + | |
| - | [[Category: Cell junction]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Coiled coil]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Exocytosis]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal binding protein-exocytosis complex]]
| + | |
| - | [[Category: Metal binding protein-protein binding complex]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Methylation]]
| + | |
| - | [[Category: Munc13]]
| + | |
| - | [[Category: Phorbol-ester binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Synapse]]
| + | |
| - | [[Category: Zinc]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
CALM1_XENLA Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ca(2+) signalling in neurons through calmodulin (CaM) has a prominent function in regulating synaptic vesicle trafficking, transport, and fusion. Importantly, Ca(2+)-CaM binds a conserved region in the priming proteins Munc13-1 and ubMunc13-2 and thus regulates synaptic neurotransmitter release in neurons in response to residual Ca(2+) signals. We solved the structure of Ca(2+)(4)-CaM in complex with the CaM-binding domain of Munc13-1, which features a novel 1-5-8-26 CaM-binding motif with two separated mobile structural modules, each involving a CaM domain. Photoaffinity labelling data reveal the same modular architecture in the complex with the ubMunc13-2 isoform. The N-module can be dissociated with EGTA to form the half-loaded Munc13/Ca(2+)(2)-CaM complex. The Ca(2+) regulation of these Munc13 isoforms can therefore be explained by the modular nature of the Munc13/Ca(2+)-CaM interactions, where the C-module provides a high-affinity interaction activated at nanomolar [Ca(2+)](i), whereas the N-module acts as a sensor at micromolar [Ca(2+)](i). This Ca(2+)/CaM-binding mode of Munc13 likely constitutes a key molecular correlate of the characteristic Ca(2+)-dependent modulation of short-term synaptic plasticity.
Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity.,Rodriguez-Castaneda F, Maestre-Martinez M, Coudevylle N, Dimova K, Junge H, Lipstein N, Lee D, Becker S, Brose N, Jahn O, Carlomagno T, Griesinger C EMBO J. 2010 Feb 3;29(3):680-91. Epub 2009 Dec 10. PMID:20010694[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rodriguez-Castaneda F, Maestre-Martinez M, Coudevylle N, Dimova K, Junge H, Lipstein N, Lee D, Becker S, Brose N, Jahn O, Carlomagno T, Griesinger C. Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca2+ and possible function in short-term synaptic plasticity. EMBO J. 2010 Feb 3;29(3):680-91. Epub 2009 Dec 10. PMID:20010694 doi:10.1038/emboj.2009.373
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