1xt3: Difference between revisions
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==Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3== | ==Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3== | ||
<StructureSection load='1xt3' size='340' side='right' caption='[[1xt3]], [[Resolution|resolution]] 2.40Å' scene=''> | <StructureSection load='1xt3' size='340' side='right' caption='[[1xt3]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1xt3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[1xt3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chinese_cobra Chinese cobra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XT3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XT3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></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=1xt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xt3 OCA], [http://pdbe.org/1xt3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xt3 RCSB], [http://www.ebi.ac.uk/pdbsum/1xt3 PDBsum]</span></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=1xt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xt3 OCA], [http://pdbe.org/1xt3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xt3 RCSB], [http://www.ebi.ac.uk/pdbsum/1xt3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xt3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 1xt3" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1xt3" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Chinese cobra]] | ||
[[Category: Chen, C J]] | [[Category: Chen, C J]] | ||
[[Category: Guan, H H]] | [[Category: Guan, H H]] | ||
Revision as of 18:40, 12 October 2017
Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3
Structural highlights
Function[3SA3_NAJAT] Basic protein that binds to cell membrane and depolarizes cardiomyocytes. This cytotoxin also possesses lytic activity on many other cells, including red blood cells (PubMed:8182052). Interaction with sulfatides in the cell membrane induces pore formation and cell internalization. Cytotoxicity is due to pore formation, and to another mechanism independent of membrane-damaging activity. When internalized, it targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. It inhibits protein kinases C. It binds to the integrin alpha-V/beta-3 (ITGAV/ITGB3) with a moderate affinity (PubMed:16407244). It also binds with high affinity to heparin (PubMed:17685633).[1] [2] [3] [4] [5] [6] [7] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAnionic citrate is a major component of venom, but the role of venom citrate in toxicity other than its inhibitory effect on the cation-dependent action of venom toxins is poorly understood. By immobilizing Chinese hamster ovary cells in microcapillary tubes and heparin on sensor chips, we demonstrated that heparan sulfate-mediated cell retention of the major cardiotoxin (CTX) from the Taiwan cobra, CTX A3, near membrane surfaces is citrate-dependent. X-ray determination of a CTX A3-heparin hexasaccharide complex structure at 2.4 A resolution revealed a molecular mechanism for toxin retention in which heparin-induced conformational changes of CTX A3 lead to citrate-mediated dimerization. A citrate ion bound to Lys-23 and Lys-31 near the tip of loop II stabilizes hydrophobic contact of the CTX A3 homodimer at the functionally important loop I and II regions. Additionally, the heparin hexasaccharide interacts with five CTX A3 molecules in the crystal structure, providing another mechanism whereby the toxin establishes a complex network of interactions that result in a strong interaction with cell surfaces presenting heparan sulfate. Our results suggest a novel role for venom citrate in biological activity and reveal a structural model that explains cell retention of cobra CTX A3 through heparan sulfate-CTX interactions. Structural basis of citrate-dependent and heparan sulfate-mediated cell surface retention of cobra cardiotoxin A3.,Lee SC, Guan HH, Wang CH, Huang WN, Tjong SC, Chen CJ, Wu WG J Biol Chem. 2005 Mar 11;280(10):9567-77. Epub 2004 Dec 6. PMID:15590643[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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