4y21: Difference between revisions

Latest revision as of 15:33, 8 November 2023

Crystal Structure of Munc13-1 MUN domain

Structural highlights

4y21 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
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

UNC-13-Munc13s have a central function in synaptic-vesicle priming through their MUN domains. However, it is unclear whether this function arises from the ability of the MUN domain to mediate the transition from the Munc18-1-closed syntaxin-1 complex to the SNARE complex in vitro. The crystal structure of the rat Munc13-1 MUN domain now reveals an elongated, arch-shaped architecture formed by alpha-helical bundles, with a highly conserved hydrophobic pocket in the middle. Mutation of two residues (NF) in this pocket abolishes the stimulation caused by the Munc13-1 MUN domain on SNARE-complex assembly and on SNARE-dependent proteoliposome fusion in vitro. Moreover, the same mutation in UNC-13 abrogates synaptic-vesicle priming in Caenorhabditis elegans neuromuscular junctions. These results support the notion that orchestration of syntaxin-1 opening and SNARE-complex assembly underlies the central role of UNC-13-Munc13s in synaptic-vesicle priming.

Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming.,Yang X, Wang S, Sheng Y, Zhang M, Zou W, Wu L, Kang L, Rizo J, Zhang R, Xu T, Ma C Nat Struct Mol Biol. 2015 Jul;22(7):547-54. doi: 10.1038/nsmb.3038. Epub 2015 Jun, 1. PMID:26030875^[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
↑ Yang X, Wang S, Sheng Y, Zhang M, Zou W, Wu L, Kang L, Rizo J, Zhang R, Xu T, Ma C. Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming. Nat Struct Mol Biol. 2015 Jul;22(7):547-54. doi: 10.1038/nsmb.3038. Epub 2015 Jun, 1. PMID:26030875 doi:https://dx.doi.org/10.1038/nsmb.3038

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] Yang X, Wang S, Sheng Y, Zhang M, Zou W, Wu L, Kang L, Rizo J, Zhang R, Xu T, Ma C. Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming. Nat Struct Mol Biol. 2015 Jul;22(7):547-54. doi: 10.1038/nsmb.3038. Epub 2015 Jun, 1. PMID:26030875 doi:https://dx.doi.org/10.1038/nsmb.3038

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[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Munc13-1 MUN domain==
-<StructureSection load='4y21' size='340' side='right' caption='[[4y21]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='4y21' size='340' side='right'caption='[[4y21]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4y21]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y21 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y21 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4y21]] is a 1 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=4Y21 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y21 FirstGlance]. <br>
-</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=4y21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y21 OCA], [http://pdbe.org/4y21 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y21 RCSB], [http://www.ebi.ac.uk/pdbsum/4y21 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y21 ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</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=4y21 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y21 OCA], [https://pdbe.org/4y21 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y21 RCSB], [https://www.ebi.ac.uk/pdbsum/4y21 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y21 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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/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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Kang, L J]]
+[[Category: Large Structures]]
-[[Category: Ma, C]]
+[[Category: Rattus norvegicus]]
-[[Category: Rizo, J]]
+[[Category: Kang LJ]]
-[[Category: Sheng, Y]]
+[[Category: Ma C]]
-[[Category: Wang, S]]
+[[Category: Rizo J]]
-[[Category: Wu, L J]]
+[[Category: Sheng Y]]
-[[Category: Xu, T]]
+[[Category: Wang S]]
-[[Category: Yang, X Y]]
+[[Category: Wu LJ]]
-[[Category: Zhang, M]]
+[[Category: Xu T]]
-[[Category: Zhang, R G]]
+[[Category: Yang XY]]
-[[Category: Zou, W J]]
+[[Category: Zhang M]]
-[[Category: Catchr]]
+[[Category: Zhang RG]]
-[[Category: Exocytosis]]
+[[Category: Zou WJ]]
-[[Category: Helical bundle]]

4y21: Difference between revisions

Latest revision as of 15:33, 8 November 2023

Crystal Structure of Munc13-1 MUN domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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