STRUCTURE AND SELF-ASSEMBLY OF A RETROVIRUS (FELV) PROLINE-RICH NEUTRALIZATION DOMAIN

The 60 amino acid proline-rich neutralization domain of the external s urface unit glycoprotein of feline leukemia virus was chemically synth esized in total and in fragments. We examined the ability of these ret roviral peptides to form ordered conformations using H-1-NMR circular dichroism spectroscopy, and intrinsic viscosity measurements. One dime nsional nuclear magnetic resonance spectroscopy revealed that the 60 a mino acid peptide could form a stable, folded structure that was long- lived, as shown by the ability to protect amide-protons in D(2)0. Pept ides corresponding to the N-terminal 42, N-terminal 20 amino acids, an d middle 20 amino acid sections could also form stable structures. The C-terminal segment did not protect any protons in D(2)0. Interestingl y, self assembly of the N-terminal 42 and C-terminal 16 amino acid pep tides into a structure very close to that of the 60 amino acid domain was observed. The circular dichroism results reveals a large negative cotton effect at 198 nm that is characteristic of the proline-rich bet a-turn helixes which consist predominantly of trans-proline. The intri nsic viscosity results suggest a non-random coil structure that is rod shaped. Our conclusion is that PRN60 forms a beta-turn helix and that this region of FeLV-gp70 is a separate folding domain of the retrovir al surface unit glycoprotein. The unique conformational properties of PRN60 and its critical role as the predominant target for neutralizing antibody responses suggest that this peptide is a reasonable candidat e for producing a synthetic peptide vaccine for FeLV.