THE AMINO-TERMINAL FUSION DOMAIN PEPTIDE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP41 INSERTS INTO THE SODIUM DODECYL-SULFATE MICELLE PRIMARILY AS HELIX WITH A CONSERVED GLYCINE AT THE MICELLE-WATER INTERFACE

A peptide based on the N-terminal fusion domain of gp41 of human immun odeficiency virus type 1 (HIV-1) and its tryptophan analog were synthe sized to examine the secondary structure in the micellar environment. Nuclear magnetic resonance (NMR), circular dichroism and electron para magnetic resonance experiments indicated that the gp41 fusion peptide inserted into the micelle primarily as a helix (59%), with substantial beta-structure (26.7%), Deep penetration of the peptide into the apol ar hydrocarbon core was supported by the results of fluorescence exper iments in which the tryptophan analog exhibited a blue shift of about 30 nm in the presence of a sodium dodecyl sulfate micelle, in 1,2-dimy ristoyl-rac-glycero-3-phosphocholine, and in 1,2-dipalmitoyl-sn-glycer o-3-phospho-L-serine vesicular solutions: The results of spin label-at tenuated H-1 resonance experiments show that the region C-terminal to G16, which contains a turn structure, exhibited substantial interactio n with the micelle, suggesting that it lies on the surface of micelle. Molecular simulation based on data from NMR experiments revealed a fl exible hinge at residues 15 and 16 (alanine and glycine, respectively) from the N terminus of the peptide located at the micelle-solution in terface. The highly conserved A15-G16 dipeptide may play a role in the function of fusion domain of HIV-1 envelope glycoprotein.