This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4cca

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Structure of human Munc18-2

Structural highlights

4cca is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

STXB2_HUMAN Familial hemophagocytic lymphohistiocytosis. The disease is caused by mutations affecting the gene represented in this entry.

Function

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.^[1] ^[2]

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.

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^[3]

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

References

↑ zur Stadt U, Rohr J, Seifert W, Koch F, Grieve S, Pagel J, Strauss J, Kasper B, Nurnberg G, Becker C, Maul-Pavicic A, Beutel K, Janka G, Griffiths G, Ehl S, Hennies HC. Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11. Am J Hum Genet. 2009 Oct;85(4):482-92. doi: 10.1016/j.ajhg.2009.09.005. PMID:19804848 doi:http://dx.doi.org/10.1016/j.ajhg.2009.09.005
↑ Cote M, Menager MM, Burgess A, Mahlaoui N, Picard C, Schaffner C, Al-Manjomi F, Al-Harbi M, Alangari A, Le Deist F, Gennery AR, Prince N, Cariou A, Nitschke P, Blank U, El-Ghazali G, Menasche G, Latour S, Fischer A, de Saint Basile G. Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells. J Clin Invest. 2009 Dec;119(12):3765-73. doi: 10.1172/JCI40732. Epub 2009 Nov 2. PMID:19884660 doi:http://dx.doi.org/10.1172/JCI40732
↑ Hackmann Y, Graham SC, Ehl S, Honing S, Lehmberg K, Arico M, Owen DJ, Griffiths GM. Syntaxin binding mechanism and disease-causing mutations in Munc18-2. Proc Natl Acad Sci U S A. 2013 Nov 5. PMID:24194549 doi:http://dx.doi.org/10.1073/pnas.1313474110

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4cca"

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CCA FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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]] 2.6&#8491;</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=4cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cca OCA], [http://pdbe.org/4cca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cca RCSB], [http://www.ebi.ac.uk/pdbsum/4cca PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cca ProSAT]</span></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 ==
-[[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.
+[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 ==
-[[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>
+[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 ==
@@ Line 27: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Arico, M]]
+[[Category: Arico M]]
-[[Category: Ehl, S]]
+[[Category: Ehl S]]
-[[Category: Graham, S C]]
+[[Category: Graham SC]]
-[[Category: Griffiths, G G]]
+[[Category: Griffiths GG]]
-[[Category: Hackmann, Y]]
+[[Category: Hackmann Y]]
-[[Category: Hoening, S]]
+[[Category: Hoening S]]
-[[Category: Lehmberg, K]]
+[[Category: Lehmberg K]]
-[[Category: Owen, D J]]
+[[Category: Owen DJ]]
-[[Category: Protein transport]]

4cca

From Proteopedia

Current revision

Structure of human Munc18-2

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox