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| | <StructureSection load='7t7r' size='340' side='right'caption='[[7t7r]], [[Resolution|resolution]] 10.00Å' scene=''> | | <StructureSection load='7t7r' size='340' side='right'caption='[[7t7r]], [[Resolution|resolution]] 10.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7t7r]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T7R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T7R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7t7r]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7T7R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7T7R FirstGlance]. <br> |
| - | </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=7t7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t7r OCA], [https://pdbe.org/7t7r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t7r RCSB], [https://www.ebi.ac.uk/pdbsum/7t7r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t7r ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 10Å</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=7t7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7t7r OCA], [https://pdbe.org/7t7r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7t7r RCSB], [https://www.ebi.ac.uk/pdbsum/7t7r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7t7r ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/UN13A_MOUSE UN13A_MOUSE]] 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. Facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (PubMed:23229896). Also involved in secretory granule priming in insulin secretion. Plays a role in dendrite formation by melanocytes (By similarity).[UniProtKB:Q62768][UniProtKB:Q9UPW8]<ref>PMID:10440375</ref> <ref>PMID:12070347</ref> <ref>PMID:15988013</ref> <ref>PMID:16644700</ref> <ref>PMID:16697276</ref> <ref>PMID:17267576</ref> <ref>PMID:17639022</ref> <ref>PMID:23229896</ref>
| + | [https://www.uniprot.org/uniprot/UN13A_MOUSE UN13A_MOUSE] 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. Facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (PubMed:23229896). Also involved in secretory granule priming in insulin secretion. Plays a role in dendrite formation by melanocytes (By similarity).[UniProtKB:Q62768][UniProtKB:Q9UPW8]<ref>PMID:10440375</ref> <ref>PMID:12070347</ref> <ref>PMID:15988013</ref> <ref>PMID:16644700</ref> <ref>PMID:16697276</ref> <ref>PMID:17267576</ref> <ref>PMID:17639022</ref> <ref>PMID:23229896</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | How can exactly six SNARE complexes be assembled under each synaptic vesicle? Here we report cryo-EM crystal structures of the core domain of Munc13, the key chaperone that initiates SNAREpin assembly. The functional core of Munc13, consisting of C1-C2B-MUN-C2C (Munc13C) spontaneously crystallizes between phosphatidylserine-rich bilayers in two distinct conformations, each in a radically different oligomeric state. In the open conformation (state 1), Munc13C forms upright trimers that link the two bilayers, separating them by approximately 21 nm. In the closed conformation, six copies of Munc13C interact to form a lateral hexamer elevated approximately 14 nm above the bilayer. Open and closed conformations differ only by a rigid body rotation around a flexible hinge, which when performed cooperatively assembles Munc13 into a lateral hexamer (state 2) in which the key SNARE assembly-activating site of Munc13 is autoinhibited by its neighbor. We propose that each Munc13 in the lateral hexamer ultimately assembles a single SNAREpin, explaining how only and exactly six SNARE complexes are templated. We suggest that state 1 and state 2 may represent two successive states in the synaptic vesicle supply chain leading to "primed" ready-release vesicles in which SNAREpins are clamped and ready to release (state 3).
| + | |
| - | | + | |
| - | Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release.,Grushin K, Kalyana Sundaram RV, Sindelar CV, Rothman JE Proc Natl Acad Sci U S A. 2022 Feb 15;119(7). pii: 2121259119. doi:, 10.1073/pnas.2121259119. PMID:35135883<ref>PMID:35135883</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 7t7r" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Grushin, K]] | + | [[Category: Mus musculus]] |
| - | [[Category: Sindelar, C V]] | + | [[Category: Grushin K]] |
| - | [[Category: Exocytosis]] | + | [[Category: Sindelar CV]] |
| - | [[Category: Membrane fusion]]
| + | |
| - | [[Category: Munc13]]
| + | |
| - | [[Category: Synaptic transmission]]
| + | |
| Structural highlights
Function
UN13A_MOUSE 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. Facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (PubMed:23229896). Also involved in secretory granule priming in insulin secretion. Plays a role in dendrite formation by melanocytes (By similarity).[UniProtKB:Q62768][UniProtKB:Q9UPW8][1] [2] [3] [4] [5] [6] [7] [8]
References
- ↑ Augustin I, Rosenmund C, Sudhof TC, Brose N. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature. 1999 Jul 29;400(6743):457-61. doi: 10.1038/22768. PMID:10440375 doi:http://dx.doi.org/10.1038/22768
- ↑ Varoqueaux F, Sigler A, Rhee JS, Brose N, Enk C, Reim K, Rosenmund C. Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):9037-42. doi:, 10.1073/pnas.122623799. Epub 2002 Jun 17. PMID:12070347 doi:http://dx.doi.org/10.1073/pnas.122623799
- ↑ Varoqueaux F, Sons MS, Plomp JJ, Brose N. Aberrant morphology and residual transmitter release at the Munc13-deficient mouse neuromuscular synapse. Mol Cell Biol. 2005 Jul;25(14):5973-84. doi: 10.1128/MCB.25.14.5973-5984.2005. PMID:15988013 doi:http://dx.doi.org/10.1128/MCB.25.14.5973-5984.2005
- ↑ Kwan EP, Xie L, Sheu L, Nolan CJ, Prentki M, Betz A, Brose N, Gaisano HY. Munc13-1 deficiency reduces insulin secretion and causes abnormal glucose tolerance. Diabetes. 2006 May;55(5):1421-9. doi: 10.2337/db05-1263. PMID:16644700 doi:http://dx.doi.org/10.2337/db05-1263
- ↑ Kang L, He Z, Xu P, Fan J, Betz A, Brose N, Xu T. Munc13-1 is required for the sustained release of insulin from pancreatic beta cells. Cell Metab. 2006 Jun;3(6):463-8. Epub 2006 May 11. PMID:16697276 doi:http://dx.doi.org/S1550-4131(06)00152-5
- ↑ Basu J, Betz A, Brose N, Rosenmund C. Munc13-1 C1 domain activation lowers the energy barrier for synaptic vesicle fusion. J Neurosci. 2007 Jan 31;27(5):1200-10. doi: 10.1523/JNEUROSCI.4908-06.2007. PMID:17267576 doi:http://dx.doi.org/10.1523/JNEUROSCI.4908-06.2007
- ↑ Kwan EP, Xie L, Sheu L, Ohtsuka T, Gaisano HY. Interaction between Munc13-1 and RIM is critical for glucagon-like peptide-1 mediated rescue of exocytotic defects in Munc13-1 deficient pancreatic beta-cells. Diabetes. 2007 Oct;56(10):2579-88. Epub 2007 Jul 16. PMID:17639022 doi:http://dx.doi.org/db06-1207
- ↑ van de Bospoort R, Farina M, Schmitz SK, de Jong A, de Wit H, Verhage M, Toonen RF. Munc13 controls the location and efficiency of dense-core vesicle release in neurons. J Cell Biol. 2012 Dec 10;199(6):883-91. doi: 10.1083/jcb.201208024. PMID:23229896 doi:http://dx.doi.org/10.1083/jcb.201208024
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