View source for 6lpc


==Crystal Structure of rat Munc18-1 with K332E/K333E mutation==
<StructureSection load='6lpc' size='340' side='right'caption='[[6lpc]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lpc]] is a 2 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=6LPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LPC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.402&#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=6lpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lpc OCA], [https://pdbe.org/6lpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lpc RCSB], [https://www.ebi.ac.uk/pdbsum/6lpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lpc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/STXB1_RAT STXB1_RAT] May participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. May play a role in determining the specificity of intracellular fusion reactions.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Priming of synaptic vesicles involves Munc13-catalyzed transition of the Munc18-1/syntaxin-1 complex to the SNARE complex in the presence of SNAP-25 and synaptobrevin-2; Munc13 drives opening of syntaxin-1 via the MUN domain while Munc18-1 primes SNARE assembly via domain 3a. However, the underlying mechanism remains unclear. In this study, we have identified a number of residues in domain 3a of Munc18-1 that are crucial for Munc13 and Munc18-1 actions in SNARE complex assembly and synaptic vesicle priming. Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18-1/syntaxin-1 complex and the MUN domain. This interaction enables the MUN domain to drive the opening of syntaxin-1 linker region, thereby leading to the extension of domain 3a and promoting synaptobrevin-2 binding. In addition, we identified two residues (K332/K333) at the bottom of domain 3a that mediate the interaction between Munc18-1 and the SNARE motif of syntaxin-1. This interaction ensures Munc18-1 to persistently associate with syntaxin-1 during the conformational change of syntaxin-1 from closed to open, which reinforces the role of Munc18-1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.

Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.,Wang X, Gong J, Zhu L, Wang S, Yang X, Xu Y, Yang X, Ma C EMBO J. 2020 Jul 9:e103631. doi: 10.15252/embj.2019103631. PMID:32643828<ref>PMID:32643828</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lpc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Syntaxin-binding protein|Syntaxin-binding protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Gong JH]]
[[Category: Ma C]]
[[Category: Wang S]]
[[Category: Wang XP]]
[[Category: Xu YY]]
[[Category: Yang XF]]
[[Category: Yang XY]]
[[Category: Zhu L]]