title: Selective effects of mastoparan analogs: separation of G-protein-directed and membrane-perturbing activities.
abstract: Mastoparan (MP), a wasp venom peptide, is known both to interact with G-proteins and to alter membrane structure and function. To determine the structural requirements for these two aspects of MP action, we constructed several analogs of the peptide and characterized them using Swiss 3T3 cell membranes. The effects of these peptides were measured on: i) G-protein-mediated stimulation of phospholipase-C activity by GTP gamma S and bombesin and ii) the membrane enzyme activities, calcium-activated phospholipase-C and Na,K-ATPase. MP strongly inhibited all the above activities and caused membrane permeabilization. Substitution of one Lys residue by Gly at either the N- or C-terminal of the MP molecule resulted in peptides which selectively inhibited G-protein stimulated phospholipase-C with no or very slight membrane-perturbing effects. Introduction of additional Lys residues to MP led to the opposite effect. Thus, G-protein modulating and membrane disrupting actions of MP appear to be not necessarily linked, and may be separated.
authors.affiliation: Clinical Biochemistry Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Danilenko
authors.forename: P
authors.initials: P
authors.lastname: Worland
authors.forename: B
authors.initials: B
authors.lastname: Carlson
authors.forename: E A
authors.initials: EA
authors.lastname: Sausville
authors.forename: Y
authors.initials: Y
authors.lastname: Sharoni
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D010455:Peptides; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000378:metabolism; D014862:Wasp Venoms / Q000494:pharmacology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D014862:Wasp Venoms; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C037500:mastoparan; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D001839:Bombesin