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Originally published In Press as doi:10.1074/jbc.M204372200 on July 18, 2002

J. Biol. Chem., Vol. 277, Issue 38, 35124-35132, September 20, 2002
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Ophioluxin, a Convulxin-like C-type Lectin from Ophiophagus hannah (King Cobra) Is a Powerful Platelet Activator via Glycoprotein VI*

Xiao-Yan DuDagger , Jeannine M. ClemetsonDagger , Alexei NavdaevDagger , Edith M. Magnenat§, Timothy N. C. Wells§, and Kenneth J. ClemetsonDagger

From the Dagger  Theodor Kocher Institute, University of Berne, CH-3012 Berne, Switzerland and § Serono Pharmaceutical Research Institute, SA, CH-1228 Geneva, Switzerland

Ophioluxin, a potent platelet agonist, was purified from the venom of Ophiophagus hannah (King cobra). Under nonreducing conditions it has a mass of 85 kDa, similar to convulxin, and on reduction gives two subunits with masses of 16 and 17 kDa, slightly larger than those of convulxin. The N-terminal sequences of both subunits are very similar to those of convulxin and other C-type lectins. Ophioluxin induces a pattern of tyrosine-phosphorylated proteins in platelets like that caused by convulxin, when using appropriate concentrations based on aggregation response, because it is about 2-4 times more powerful as agonist than the latter. Ophioluxin and convulxin induce [Ca2+]i elevation both in platelets and in Dami megakaryocytic cells, and each of these C-type lectins desensitizes responses to the other. Convulxin agglutinates fixed platelets at 2 µg/ml, whereas ophioluxin does not, even at 80 µg/ml. Ophioluxin resembles convulxin more than echicetin or alboaggregin B because polyclonal anti-ophioluxin antibodies recognize both ophioluxin and convulxin, but not echicetin, and platelets adhere to and spread on ophioluxin- or convulxin-precoated surfaces in the same way that is clearly different from their behavior on an alboaggregin B surface. Immobilized ophioluxin was used to isolate the glycoprotein VI-Fcgamma complex from resting platelets, which also contained Fyn, Lyn, Syk, LAT, and SLP76. Ophioluxin is the first multiheterodimeric, convulxin-like snake C-type lectin, as well as the first platelet agonist, to be described from the Elapidae snake family.


* This work was supported by Grant 31-063868.00 (to K. J. C.) from the Swiss National Science Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Theodor Kocher Inst., University of Berne, Freiestrasse 1, CH-3012 Berne, Switzerland. Tel.: 41-31-631-41-48; Fax: 41-31-921-54-43; E-mail: clemetson@tki.unibe.ch.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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