Carditoxins (CTXs) from cobra snake venoms, the basic 60-62 residue all-bet
a sheet polypeptides, are known to bind to and impair the function of cell
membranes. To assess the membrane induced conformation and orientation of C
TXs, the interaction of the P-type cardiotoxin II from Naja oxiana snake ve
nom (CTII) with perdeuterated dodecylphosphocholine (DPC) was studied using
H-1-NMR spectroscopy and diffusion measurements. Under conditions where th
e toxin formed a well-defined complex with DPC, the spatial structure of CT
II with respect to the presence of tightly bound water molecules in loop II
, was calculated using the torsion angle dynamics program DYANA. The struct
ure was found to be similar, except for subtle changes in the tips of all t
hree loops, to the previously described "major" form of CTII in aqueous sol
ution illustrated by the "trans" configuration of the Val7-Pro8 peptide bon
d. No "minor" form with the "cis" configuration of the above bond was found
in the micelle-bound state. The broadening of the CTII backbone proton sig
nals by 5, 16-doxylstearate relaxation probes, together with modeling based
on the spatial structure of CTII, indicated a periphery mode of binding of
the toxin molecule to the micelle and revealed its micelle interacting dom
ain. The latter includes a hydrophobic region of CTII within the extremitie
s of loops I and III (residues 5-11, 46-50), the basement of loop II (resid
ues 24-29,31-37) and the belt of polar residues encircling these loops (lys
ines 4,5,12,23,50, serines 11,46, histidine 31, arginine 36). It is suggest
ed that this structural motif and the mode of binding can be realized durin
g interaction of CTXs with lipid and biological membranes. (C) 2001 Academi
c Press.