Alboluxin, a snake C-type lectin from Trimeresurus albolabris venom is a potent platelet agonist acting via GPIb and GPVI.
Alboluxin, a potent platelet activator, was purified from Trimeresurus albolabris venom with a mass of 120 kDa non-reduced and, after reduction, subunits of 17 and 24 kDa. Alboluxin induced a tyrosine phosphorylation profile in platelets that resembles those produced by collagen and convulxin, involving the time dependent tyrosine phosphorylation of Fc receptor gamma chain (Fc gamma), phospholipase Cgamma2 (PLCgamma2), LAT and p72SYK. Antibodies against both GPIb and GPVI inhibited platelet aggregation induced by alboluxin, whereas antibodies against alpha2beta1 had no effect. Inhibition of alphaIIb beta3 reduced the aggregation response to alboluxin, as well as tyrosine phosphorylation of platelet proteins, showing that activation of alphaIIb beta3 and binding of fibrinogen are involved in alboluxin-induced platelet aggregation and it is not simply agglutination. N-terminal sequence data from the beta-subunit of alboluxin indicates that it belongs to the snake C-type lectin family. The C-type lectin subunits are larger than usual possibly due to post-translational modifications such as glycosylation. Alboluxin is a hexameric (alphabeta)3 snake C-type lectin which activates platelets via both GPIb and GPVI.
Du Xiao-Yan
Theodor Kocher Institute, University of Berne, Switzerland.
Magnenat
Edith
E
Wells
Timothy N C
TN
Clemetson
Kenneth J
KJ
D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019921:Biotinylation; D002352:Carrier Proteins; D002852:Chromatography, Ion Exchange; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000302:isolation & purification* / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021122:Protein Subunits; D011506:Proteins / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013268:Stimulation, Chemical; D014757:Viper Venoms
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D003435:Crotalid Venoms; D037102:Lectins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D021122:Protein Subunits; D011506:Proteins; C029748:Trimeresurus venoms; D014757:Viper Venoms; C469547:alboluxin protein, Trimeresurus albolabris; C098341:platelet membrane glycoprotein VI; C080995:echicetin; D004533:Egtazic Acid; D004492:Edetic Acid; D000527:Alprostadil