Ophioluxin, a convulxin-like C-type lectin from Ophiophagus hannah (King cobra) is a powerful platelet activator via glycoprotein VI.
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 [Ca(2+)](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 microg/ml, whereas ophioluxin does not, even at 80 microg/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.
Theodor Kocher Institute, University of Berne, CH-3012 Berne, Switzerland.
Xiao-Yan
XY
Du
Jeannine M
JM
Clemetson
Alexei
A
Navdaev
Edith M
EM
Magnenat
Timothy N C
TN
Wells
Kenneth J
KJ
Clemetson
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003435:Crotalid Venoms / Q000494:pharmacology; D004546:Elapid Venoms / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D017815:Elapidae; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D037181:Lectins, C-Type; D008969:Molecular Sequence Data; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D003435:Crotalid Venoms; D004546:Elapid Venoms; D037102:Lectins; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; C466774:ophioluxin, Ophiophagus hannah; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D003094:Collagen