4cca: Difference between revisions

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-{{STRUCTURE_4cca|  PDB=4cca  |  SCENE=  }}
-===Structure of human Munc18-2===
-==Disease==
+==Structure of human Munc18-2==
-[[http://www.uniprot.org/uniprot/STXB2_HUMAN STXB2_HUMAN]] Familial hemophagocytic lymphohistiocytosis. The disease is caused by mutations affecting the gene represented in this entry.
+<StructureSection load='4cca' size='340' side='right'caption='[[4cca]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4cca]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CCA 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]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=4cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cca OCA], [https://pdbe.org/4cca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cca RCSB], [https://www.ebi.ac.uk/pdbsum/4cca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cca ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/STXB2_HUMAN STXB2_HUMAN] Familial hemophagocytic lymphohistiocytosis. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/STXB2_HUMAN STXB2_HUMAN] Involved in intracellular vesicle trafficking and vesicle fusion with membranes. Contributes to the granule exocytosis machinery through interaction with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that regulate membrane fusion. Regulates cytotoxic granule exocytosis in natural killer (NK) cells.<ref>PMID:19804848</ref> <ref>PMID:19884660</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Mutations in either syntaxin 11 (Stx11) or Munc18-2 abolish cytotoxic T lymphocytes (CTL) and natural killer cell (NK) cytotoxicity, and give rise to familial hemophagocytic lymphohistiocytosis (FHL4 or FHL5, respectively). Although Munc18-2 is known to interact with Stx11, little is known about the molecular mechanisms governing the specificity of this interaction or how in vitro IL-2 activation leads to compensation of CTL and NK cytotoxicity. To understand how mutations in Munc18-2 give rise to disease, we have solved the structure of human Munc18-2 at 2.6 A resolution and mapped 18 point mutations. The four surface mutations identified (R39P, L130S, E132A, P334L) map exclusively to the predicted syntaxin and soluble N-ethylmaleimide-sensitive factor accessory protein receptor binding sites of Munc18-2. We find that Munc18-2 binds the N-terminal peptide of Stx11 with a approximately 20-fold higher affinity than Stx3, suggesting a potential role in selective binding. Upon IL-2 activation, levels of Stx3 are increased, favoring Munc18-2 binding when Stx11 is absent. Similarly, Munc18-1, expressed in IL-2-activated CTL, is capable of binding Stx11. These findings provide potential explanations for restoration of Munc18-Stx function and cytotoxicity in IL-2-activated cells.
-==Function==
+Syntaxin binding mechanism and disease-causing mutations in Munc18-2.,Hackmann Y, Graham SC, Ehl S, Honing S, Lehmberg K, Arico M, Owen DJ, Griffiths GM Proc Natl Acad Sci U S A. 2013 Nov 5. PMID:24194549<ref>PMID:24194549</ref>
-[[http://www.uniprot.org/uniprot/STXB2_HUMAN STXB2_HUMAN]] Involved in intracellular vesicle trafficking and vesicle fusion with membranes. Contributes to the granule exocytosis machinery through interaction with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that regulate membrane fusion. Regulates cytotoxic granule exocytosis in natural killer (NK) cells.<ref>PMID:19804848</ref> <ref>PMID:19884660</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4cca]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CCA OCA].
+</div>
+<div class="pdbe-citations 4cca" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-<references group="xtra"/><references/>
+*[[Syntaxin-binding protein|Syntaxin-binding protein]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arico, M.]]
+[[Category: Large Structures]]
-[[Category: Ehl, S.]]
+[[Category: Arico M]]
-[[Category: Graham, S C.]]
+[[Category: Ehl S]]
-[[Category: Griffiths, G G.]]
+[[Category: Graham SC]]
-[[Category: Hackmann, Y.]]
+[[Category: Griffiths GG]]
-[[Category: Hoening, S.]]
+[[Category: Hackmann Y]]
-[[Category: Lehmberg, K.]]
+[[Category: Hoening S]]
-[[Category: Owen, D J.]]
+[[Category: Lehmberg K]]
-[[Category: Protein transport]]
+[[Category: Owen DJ]]