Immunogenic peptides corresponding to the dominant antigenic region alanine-597 to cysteine-619 in the transmembrane protein of simian immunodeficiency virus have a propensity to fold in aqueous solution.
Two synthetic peptides corresponding to the N- and C-terminal halves of a 23 amino acid sequence representing an immunodominant domain of the simian immunodeficiency virus of macaque origin (SIVmac) were examined for conformational preferences in aqueous solution by proton nuclear magnetic resonance methods. The two constituent peptides, termed A12-7 (Ala597-Ile-Glu-Lys-Tyr-Leu-Glu-Asp-Gln-Ala-Gln607) and A12-9 (Leu608-Asn-Ala-Trp-Gly-Cys-Ala-Phe-Arg-Gln-Val-Ser619), were found to contain a considerable conformational preference for states in which the backbone phi and psi angles populate the alpha region of the Ramachandran plot. Further, for peptide A12-9, the types and intensities of the nuclear Overhauser effect (NOE) connectivities between protons in the polypeptide backbone suggest that these states appear to include helical turns. The temperature dependence of the amide proton chemical shifts indicates that some degree of intramolecular hydrogen bonding occurs in these peptides. These results are consistent with a model in which immunogenic peptides which induce antibodies reactive with the intact protein from which the peptide sequence was derived contain conformational preferences in water solution for states other than the extended-chain forms typically found in "random coil" peptides.
Dyson
H J
HJ
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.
Norrby
E
E
Hoey
K
K
Parks
D E
DE
Lerner
R A
RA
Wright
P E
PE
D000409:Alanine / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D003429:Cross Reactions; D003545:Cysteine / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000276:immunology; D008251:Macaca; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D011817:Rabbits; D015302:Simian Immunodeficiency Virus / Q000737:chemistry* / Q000276:immunology; D012996:Solutions; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D012996:Solutions; D014759:Viral Envelope Proteins; D003545:Cysteine; D000409:Alanine