Conformational state of a 25-mer peptide from the cyclophilin-binding loop 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 microM. This peptide corresponds to the Cyp18-binding domain of HIV-1 Gag. A replacement of Gly with Ala in the cyclophilin-binding loop of HIV-1 Gag polyprotein results in the prevention of the packaging of Cyp18 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 implicates the existence of a stabilizing structure, we were not able to detect secondary structure formation by 1H-NMR and CD spectroscopy. We characterized the peptide as a substrate for Cyp18 by two-dimensional exchange 1H-NMR spectroscopy. Surprisingly, we found similar binding characteristics for a peptide corresponding to 25-mer peptide containing the above-mentioned Gly to Ala substitution.
Reimer
U
U
Max-Planck-Gesellschaft, Forschungsstelle Enzymologie der Proteinfaltung, Halle/S., Federal Republic of Germany.
Drewello
M
M
Jakob
M
M
Fischer
G
G
Schutkowski
M
M
D000595:Amino Acid Sequence; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008715:Methionine; D008969:Molecular Sequence Data; D009646:Norleucine; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012996:Solutions
D016655:HIV Core Protein p24; D010446:Peptide Fragments; D012996:Solutions; D009646:Norleucine; D008715:Methionine; D019696:Peptidylprolyl Isomerase