title: Alboaggregins A and B. Structure and interaction with human platelets.
abstract: Viper venoms contain a variety of platelet binding proteins including those which bind to platelet GPIb/GPIX. Most of these proteins inhibit von Willebrand factor mediated platelet agglutination. Here we report the primary structures of unique members of this family, alboaggregins A and B, isolated from Trimeresurus albolabris, which have the ability to stimulate platelet agglutination and aggregation. Four chains of alboaggregin A and two chains of alboaggregin B share a high degree of homology and all cysteines in both alboaggregins are conserved. Both alboaggregins caused similar agglutination of fixed platelets. Alboaggregin A induced platelet aggregation and release reaction with EC50 = 10 and 30 nM, respectively, which is 20-fold lower than those for alboaggregin B. These observations suggest that the dimeric structure of alboaggregin B is sufficient to mediate its binding to GPIb and induce agglutination of platelets whereas aggregation and release reaction are significantly enhanced by tetrameric structure of alboaggregin A.
authors.affiliation: Department of Physiology, Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA. kowalska@kermit.oncol.chop.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Kowalska
authors.forename: L
authors.initials: L
authors.lastname: Tan
authors.forename: J C
authors.initials: JC
authors.lastname: Holt
authors.forename: M
authors.initials: M
authors.lastname: Peng
authors.forename: J
authors.initials: J
authors.lastname: Karczewski
authors.forename: J J
authors.initials: JJ
authors.lastname: Calvete
authors.forename: S
authors.initials: S
authors.lastname: Niewiarowski
mesh_terms: D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D003435:Crotalid Venoms / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D003435:Crotalid Venoms; D010975:Platelet Aggregation Inhibitors; C112003:alboaggregin A; C112004:alboaggregin B