EFFECT OF THE CONFORMATION OF A PEPTIDE FROM GP41 ON BINDING AND DOMAIN FORMATION IN MODEL MEMBRANES

Binding of the peptide fragment 828-848 (P828), amino acid sequence RV IEVVQGACRAIRHIPRRIR, from the carboxy-terminal region of the envelope glycoprotein gp41 of human immunodeficiency virus type 1 (HIV-1) to me mbranes composed of a mixture of neutral and negatively charged phosph olipids results in domain or cluster formation of the charged lipid. T he conformation and dynamics of the peptide are investigated in soluti on and in the presence of sodium dodecyl sulphate (SDS) micelles using high resolution nuclear magnetic resonance (NMR) spectroscopy and cir cular dichroism (CD) spectropolarimetry. The CD results demonstrate th at addition of either SDS, negatively charged phospholipid liposomes, or trifluoroethanol (TFE) induces a conformational transition of the p eptide from a random coil or an extended chain in water to a more orde red structure with an estimated helical content of up to 60%. The stru cture of the peptide in a membrane mimetic SDS solution was investigat ed in detail using two-dimensional NMR. The measurements demonstrate t he existence of a helical component in the peptide conformation in the SDS bound state. The peptide most likely exists as an ensemble of con formations with exchange times between them which are fast on the chem ical shift NMR time scale (10(-3) s). Simple neutralization of the six arginine sidechain charges does not cause the peptide to adopt an ord ered structure. Thus, there is an additional requirement for the struc tural transition such as that resulting from constraint of the peptide on a surface, or localization of the peptide at the lipid-water inter face where the polarity is lower. Our results favour a model of the pe ptide-lipid interaction in which the peptide backbone is located in th e water phase and part of the amino acid sidechains penetrate the lipi d-water interface.