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5ue8

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The crystal structure of Munc13-1 C1C2BMUN domain

Structural highlights

5ue8 is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5uf7
Gene:	Unc13a, Unc13h1 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Munc13-1 acts as a master regulator of neurotransmitter release, mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes. It is unclear how the functions of the multiple domains of Munc13-1 are coordinated. The crystal structure of a Munc13-1 fragment including its C1, C2B and MUN domains (C1C2BMUN) reveals a 19.5 nm-long multi-helical structure with the C1 and C2B domains packed at one end. The similar orientations of the respective diacyglycerol- and Ca2+-binding sites of the C1 and C2B domains suggest that the two domains cooperate in plasma-membrane binding and that activation of Munc13-1 by Ca2+ and diacylglycerol during short-term presynaptic plasticity are closely interrelated. Electrophysiological experiments in mouse neurons support the functional importance of the domain interfaces observed in C1C2BMUN. The structure imposes key constraints for models of neurotransmitter release and suggests that Munc13-1 bridges the vesicle and plasma membranes from the periphery of the membrane-membrane interface.

Mechanistic Insights into Neurotransmitter Release and Presynaptic Plasticity from the Crystal Structure of Munc13-1 C1C2BMUN.,Xu J, Camacho M, Xu Y, Esser V, Liu X, Trimbuch T, Pan YZ, Ma C, Tomchick DR, Rosenmund C, Rizo J Elife. 2017 Feb 8;6. pii: e22567. doi: 10.7554/eLife.22567. PMID:28177287^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Betz A, Ashery U, Rickmann M, Augustin I, Neher E, Sudhof TC, Rettig J, Brose N. Munc13-1 is a presynaptic phorbol ester receptor that enhances neurotransmitter release. Neuron. 1998 Jul;21(1):123-36. PMID:9697857
↑ Betz A, Thakur P, Junge HJ, Ashery U, Rhee JS, Scheuss V, Rosenmund C, Rettig J, Brose N. Functional interaction of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle priming. Neuron. 2001 Apr;30(1):183-96. PMID:11343654
↑ Rhee JS, Betz A, Pyott S, Reim K, Varoqueaux F, Augustin I, Hesse D, Sudhof TC, Takahashi M, Rosenmund C, Brose N. Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs. Cell. 2002 Jan 11;108(1):121-33. PMID:11792326
↑ Xu J, Camacho M, Xu Y, Esser V, Liu X, Trimbuch T, Pan YZ, Ma C, Tomchick DR, Rosenmund C, Rizo J. Mechanistic Insights into Neurotransmitter Release and Presynaptic Plasticity from the Crystal Structure of Munc13-1 C1C2BMUN. Elife. 2017 Feb 8;6. pii: e22567. doi: 10.7554/eLife.22567. PMID:28177287 doi:http://dx.doi.org/10.7554/eLife.22567

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ue8"

@@ Line 3: / Line 3: @@
 <StructureSection load='5ue8' size='340' side='right' caption='[[5ue8]], [[Resolution|resolution]] 3.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ue8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UE8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UE8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ue8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UE8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UE8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uf7|5uf7]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Unc13a, Unc13h1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ue8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ue8 OCA], [http://pdbe.org/5ue8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ue8 RCSB], [http://www.ebi.ac.uk/pdbsum/5ue8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ue8 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
 [[Category: Rizo, J]]
 [[Category: Tomchick, D R]]

5ue8

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Current revision

The crystal structure of Munc13-1 C1C2BMUN domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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