Myotoxic class II phospholipases A(2) from snake venoms can be divided into Asp49
and Lys49 types. The latter, including Bothrops asper myotoxin II, exert membrane
damage despite lacking catalytic activity. A heparin-binding, hydrophobic/cationic
region, near the C-terminus of myotoxin II (115-129) has been shown to be relevant
in its membrane-damaging actions. However, some observations suggest also a potential
participation of its N-terminal region. An immunochemical approach was utilized to
examine the properties and possible role in toxicity of the N-terminal helix of myotoxin
II. Rabbit antibodies raised to a synthetic peptide comprising residues 1-15 recognized
the native protein. These antibodies were utilized to compare the antigenic characteristics
of the N-terminal helix of several myotoxic phospholipases A(2), showing generally
stronger binding to Lys49 myotoxins, in comparison to Asp49 counterparts. However,
three Lys49 myotoxins (Cerrophidion godmani myotoxin II, Atropoides nummifer myotoxin
II, and Trimeresurus flavoviridis basic protein I) were not recognized by the antibodies,
revealing a significant antigenic variability of the N-terminal region within this
group of toxins. In neutralization experiments, pre-incubation of myotoxin II with
affinity-purified antibodies to the N-terminal helix did not inhibit its myotoxic
activity in mice, nor its cytotoxic effect upon cultured muscle cells. These findings
argue against a critical role of the N-terminal region of this protein in toxicity.
Thus, the precise role of the N-terminal helix of myotoxin II and related Lys49 phospholipases
A(2), regarding their toxic mechanisms, remains controversial, and requires further
experimental study to be clarified.