Open AccessThe C‐terminal region of ammodytoxins is important but not sufficient for neurotoxicity
Author(s) -
Prijatelj Petra,
Križaj Igor,
Kralj Bogdan,
Gubenšek Franc,
Pungerčar Jože
Publication year - 2002
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2002.03301.x
Subject(s) - neurotoxicity , receptor , venom , chemistry , calmodulin , biochemistry , microbiology and biotechnology , toxicity , biology , enzyme , organic chemistry
Ammodytoxins (Atxs) are presynaptically acting snake venom phospholipase A 2 (PLA 2 ) toxins the molecular mechanism of whose neurotoxicity is not completely understood. Two chimeric PLA 2 s were prepared by replacing the C‐terminal part of a nontoxic venom PLA 2 , ammodytin I 2 , with that of AtxA(K108N). The chimeras were not toxic, but were able to bind strongly to an Atxs‐specific neuronal receptor, R25. They also showed an increased affinity for calmodulin, a recently identified high‐affinity binding protein for Atxs, whereas affinity for a neuronal M‐type PLA 2 receptor remained largely unchanged. The results show that the C‐terminal region of Atxs, which is known to be involved in neurotoxicity, is critical for their interaction with specific binding proteins, but that some other part of the molecule also contributes to toxicity.