1XT3

Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3

Summary for 1XT3

• Entry DOI: 10.2210/pdb1xt3/pdb
• Descriptor: Cytotoxin 3, 2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose, CITRIC ACID, ... (4 entities in total)
• Functional Keywords: ctx-3, heparin, citrate, toxin
• Biological source: Naja atra (Chinese cobra)
• Cellular location: Secreted : P60301
• Total number of polymer chains: 2
• Total formula weight: 15459.21

Authors

Lee, S.-C.,Guan, H.-H.,Wang, C.-H.,Huang, W.-N.,Chen, C.-J.,Wu, W.-G. (deposition date: 2004-10-21, release date: 2004-12-14, Last modification date: 2024-10-09)

Primary citation

Lee, S.-C.,Guan, H.-H.,Wang, C.-H.,Huang, W.-N.,Tjong, S.-C.,Chen, C.-J.,Wu, W.-G.
Structural basis of citrate-dependent and heparan sulfate-mediated cell surface retention of cobra cardiotoxin A3
J.Biol.Chem., 280:9567-9577, 2005

PubMed Abstract: 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.

PubMed: 15590643
DOI: 10.1074/jbc.M412398200

Experimental method

X-RAY DIFFRACTION (2.4 Å)