The FLG motif in the N-terminal region of glucoprotein 41 of human immunodeficiency virus type 1 adopts a type-I beta turn in aqueous solution and serves as the initiation site for helix formation.

NMR and CD studies were carried out on a peptide representing the hydrophobic N-terminal domain of envelope glycoprotein of human immunodeficiency virus type-1 in solutions of varying polarity. It was found that in aquaeous solution the amide proton of glycine in the FLG motif resonated at a considerably high field and its chemical shift, within the limit of experimental precision, had a temperature coefficient of zero in the range studied. The upfield shift of NH of the glycine could be largely attributed to the ring-current effect of phenylalanine in the FLG motif that participated in a type-1 beta turn with a short Cbeta(i)-NH(i+2) distance. The slower proton-deuterion exchange for the glycine amide proton relative to that of other glycines was consistent with a folded structure for the motif in aquaeous solution. Results of the molecular simulation showed that this proton was shielded from the solvent by non-polar side chains of the amino acid residues surrounding the turn stabilized by hydrophobic interactions, thus explaining the zero temperature coefficient of the proton chemical shift. The structural stabilizing effect of the hydrophobic interaction was supported by the behavior of the proton in less polar Me2SO solution, in which the anomaly in the chemical shift and its temperature coefficient was less prominent. Detailed secondary-structure analysis suggested that the beta turn of the FLG motif may act as an initiation core for helix formation, probably because the turn readily transforms into helical form.