1xt3
Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3
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OverviewOverview
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 StructureAbout this Structure
1XT3 is a Single protein structure of sequence from Naja atra with CIT as ligand. Full crystallographic information is available from OCA.
ReferenceReference
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
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