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1xt3
From Proteopedia
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[[Image:1xt3.gif|left|200px]] | [[Image:1xt3.gif|left|200px]] | ||
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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''' | ||
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[[Category: Wang, C H.]] | [[Category: Wang, C H.]] | ||
[[Category: Wu, W G.]] | [[Category: Wu, W G.]] | ||
| - | [[Category: | + | [[Category: Citrate]] |
| - | [[Category: | + | [[Category: Ctx-3]] |
| - | [[Category: | + | [[Category: Heparin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:28:38 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 12:28, 3 May 2008
Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3
Overview
Anionic 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.
About this Structure
1XT3 is a Single protein structure of sequence from Naja atra. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sat May 3 15:28:38 2008
Categories: Naja atra | Single protein | Chen, C J. | Guan, H H. | Huang, W N. | Lee, S C. | Wang, C H. | Wu, W G. | Citrate | Ctx-3 | Heparin
