STRUCTURAL FEATURES OF AMPHIPATHIC PEPTIDES REQUIRED FOR THE ACTIVATION OF G-PROTEINS
Aljoša Bavec, Ursel Soomets, Ulo LAngel and Matjaž Zorko, Institute of Biochemistry, Medical Faculty, Ljubljana, Slovenia Dept. Neurocjem. Neurotox., Stockholm University, Stockholm, Sweden
Eight different amphipathic peptides were tested as modulators of GTPase activity of G-proteins from rat brain cortex membranes: mastoparan and melittin (components of wasp and bee venom, respectively), MAS17 (inactive mastoparan analog), M252 and M256 (peptides derived from nerve growth factor receptor), PD1 (synthetic peptide detergent), M366 (peptide derived from b-amyloid protein) and cys-pAntp (homeodomain part of Drosophila antennapedia protein). Four of the peptides (mastoparan, melittin, PD1 and M366) increased GTPase activity, other peptides showed no effect. Correlation of these data with peptide sequences, their predicted secondary structure and residue solvent accessibility pointed to two types of activators. First type (melittin and PD1) is characterised by longer (24-26 amino acids) fully amphipathic helical structure with separated charges at both ends of the sequence. Second type of activators (mastoparan and M366) is a shorter helix (11-14 amino acids) and contains a motif consisted of lysine in position 4, followed by 5 to 6 amino acids with the residues of low solvent accessibility.