Conformation of a T-cell stimulating peptide of interleukin-1 beta protein: circular dichroism studies.
A T-cell stimulating peptide Val-Gln-Gly-Glu-Glu-Ser-Asn-Asp-Lys-OH, the 163-171 fragment epitope of interleukin-1 beta (IL-1 beta), has been synthesized in solution phase and purified by reverse-phase high-performance liquid chromatography (RP-HPLC). The backbone conformation of the synthetic fragment, investigated in aqueous solution by circular dichroism (CD) spectroscopy, is qualitatively a mixture of beta-turns and random coil. Quantification of the CD spectra revealed the presence of a 9% beta-turn fraction in water at pH 7.0, suggesting the occurrence of the conformation for the epitope fragment in aqueous solution necessary for T-cell stimulation and antigenicity. Concomitant changes in CD spectra were observed with increases in the trifluoroethanol (TFE) concentration in water, and the beta-turn fraction in peptide increased to 28% at a concentration of 90% TFE. This helicogenic solvent, as well as other solvents such as methanol, acetonitrile and dioxane (all favouring an ordered structure in peptides), failed to induce any alpha-helical conformation in the IL-1 beta (163-171) fragment, and CD spectra were attributed to only beta-turn ordered structure. This beta-turn structure has also been found to be a theoretically preferred conformation using Chou-Fasman proclivity data and is in accordance with the presence of an all-beta-globular conformation for its parent molecule IL-1 beta. Thus, the beta-turn conformation is probably involved in retention of T-cell stimulation activity in this synthetic epitope.
Siddiqui
M Z
MZ
Peptide Synthesis Laboratory (NBC), Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh.
Sharma
A K
AK
Kumar
S
S
Kumar
A
A
Bhat
P N
PN
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry; D007375:Interleukin-1 / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D053583:Interleukin-1beta; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects
D000939:Epitopes; D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; C052994:interleukin-1beta (163-171)