Structural features of amphipathic peptides required for the activation ofG-proteins

Eight different amphipathic peptides were tested as modulators of GTPase ac tivity of G-proteins from rat brain cortex membranes: mastoparan and melitt in (components of wasp and bee venom, respectively), MAS17 (inactive mastop aran analog), M252 and M256 (peptides derived from nerve growth factor rece ptor), PD1 (synthetic peptide detergent), M366 (peptide derived from beta-a myloid protein) and cys-pAntp (homeodomain part of Drosophila antennapedia protein). Four of the peptides (mastoparan, melittin, PD1 and M366) increas ed GTPase activity, other peptides showed no effect. Correlation of these d ata with peptide sequences, their predicted secondary structure and residue solvent accessibility pointed to two types of activators. First type (meli ttin and PD1) is characterised by longer (24-26 amino acids) fully amphipat hic helical structure with separated charges at both ends of the sequence. Second type of activators (mastoparan and M366) is a shorter helix (11-14 a mino acids) and contains a motif consisted of lysine in position 4, followe d by 5 to 6 amino acids with the residues of low solvent accessibility.