Orientation and effects of mastoparan X on phospholipid bicelles.
Mastoparan X (MPX: INWKGIAAMAKKLL-NH2) belongs to a family of ionophoric peptides found in wasp venom. Upon binding to the membrane, MPX increases the cell's permeability to cations leading to a disruption in the electrolyte balance and cell lysis. This process is thought to occur either through a membrane-thinning mechanism, where the peptide resides on the membrane surface thereby disrupting lipid packing, or through formation of an oligomeric pore. To address this issue, we have used both high-resolution and solid-state 2H NMR techniques to study the structure and orientation of MPX when associated with bicelles. NOESY and chemical shift analysis showed that in bicelles, MPX formed a well-structured amphipathic alpha-helix. In zwitterionic bicelles, the helical axis was found to rest generally perpendicular to the membrane normal, which could be consistent with the "carpet" mechanism for lytic activity. In anionic bicelles, on the other hand, the helical axis was generally parallel to the membrane normal, which is more consistent with the pore model for lytic activity. In addition, MPX caused significant disruption in lipid packing of the negatively charged phospholipids. Taken together, these results show that MPX associates differently with zwitterionic membranes, where it rests parallel to the surface, compared with negatively charged membranes, where it penetrates longitudinally.
Whiles
J A
JA
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California 92093, USA.
Brasseur
R
R
Glover
K J
KJ
Melacini
G
G
Komives
E A
EA
Vold
R R
RR
D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010743:Phospholipids / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014862:Wasp Venoms / Q000737:chemistry* / Q000494:pharmacology*
D036341:Intercellular Signaling Peptides and Proteins; D008823:Micelles; D010455:Peptides; D010743:Phospholipids; D014862:Wasp Venoms; C071123:mastoparan X