CONFORMATIONAL STATE OF A 25-MER PEPTIDE FROM THE CYCLOPHILIN-BINDINGLOOP OF THE HIV TYPE-1 CAPSID PROTEIN

Recently a 25-residue part of Gag polyprotein from HIV type 1 (HIV-1) was reported to bind to the cytosolic 18 kDa cyclophilin (Cyp18) with an IC50 value of 180 mu M. This peptide corresponds to the Cyp18-bindi ng domain of HIV-1 Gag. A replacement of Gly with Ala in the cyclophil in-binding loop of HIV-1 Gag polyprotein results in the prevention of the packaging of Cyp 18 into virions. We found only two conformers of this peptide among 16 possible expected conformers, owing to cis/trans isomerization of four peptidyl-prolyl bonds, Although this finding Im plicates the existence of a stabilizing structure, we were not able to detect secondary structure formation by H-1-NMR and CD spectroscopy. We characterized the peptide as a substrate for Cyp18 by two-dimension al exchange H-1-NMR spectroscopy. Surprisingly, we found similar bindi ng characteristics for a peptide corresponding to 25-mer peptide conta ining the above-mentioned Gly to Ala substitution.