Snake-venom phospholipase A2 neurotoxins. Potentiation of a single-chain neurotoxin by the chaperon subunit of a two-component neurotoxin.
The venoms from Crotalinae and Viperinae snakes contain only two kinds of phospholipase A2 neurotoxins (beta-neurotoxins): single-chain beta-neurotoxins, such as agkistrodotoxin and ammodytoxin-A, and dimeric beta-neurotoxins, which, in the case of the best studied ones, crotoxin-like toxins, consist of the non-covalent association of a phospholipase A2 (CB) and a non-enzymatic chaperon (CA). Possible evolutionary relationships of these beta-neurotoxins have been investigated by analyzing whether CA could behave as a chaperon toward agkistrodotoxin and ammodytoxin, as it does in the crotoxin complex. CA increased the lethal potency of agkistrodotoxin and modified its pharmacological effect on Torpedo synaptosomes. Sedimentation experiments proved that CA can form an heterocomplex with agkistrodotoxin. Agkistrodotoxin prevented the binding to CA of an anti-CA mAb which recognizes an epitope at the zone of interaction between crotoxin subunits, suggesting the association of CA and agkistrodotoxin implicated the same zone. A 10-fold molar excess of CA over ammodytoxin modified the effect of ammodytoxin on acetylcholine release but did not increase the lethal potency of ammodytoxin. Sedimentation experiments showed CA and ammodytoxin can form an heterocomplex which is less stable than CA.agkistrodotoxin. Ammodytoxin A did not compete with the anti-CA mAb. These observations are in good agreement with the sequence similarities between CB and agkistrodotoxin (80%) and ammodytoxin A (60%).
Choumet
V
V
Unité des Venins, Unité associée Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Saliou
B
B
Fideler
L
L
Chen
Y C
YC
Gubensek
F
F
Bon
C
C
Delot
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003435:Crotalid Venoms / Q000737:chemistry / Q000633:toxicity*; D003439:Crotoxin / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D004357:Drug Synergism; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity*; D010741:Phospholipases A / Q000737:chemistry / Q000633:toxicity*; D054467:Phospholipases A2; D017386:Sequence Homology, Amino Acid; D013574:Synaptosomes / Q000187:drug effects; D014101:Torpedo; D014757:Viper Venoms / Q000737:chemistry / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D003435:Crotalid Venoms; D046911:Macromolecular Substances; D009498:Neurotoxins; D014757:Viper Venoms; C070121:beta-agkistrodotoxin; D003439:Crotoxin; C068117:ammodytoxin A; D010741:Phospholipases A; D054467:Phospholipases A2