Biomolecular mirror-image recognition: reciprocal chiral-specific DNA binding of synthetic enantiomers of zinc finger domain from GAGA factor.
To experimentally demonstrate the mirror-image recognition in protein and DNA interaction, we have designed a small DNA-binding peptide based on the zinc-finger domain of GAGA transcription factor. Circular dichroism data suggest that the conformations of peptide enantiomers as well as the DNA enantiomers have a mirror-image relationship. The gel mobility shift assay showed that the synthetic enantiomers of the peptide showed reciprocal chiral-specific interactions with the DNA; the natural L-peptide binds specifically with the natural D-DNA substrate, and the unnatural D-peptide binds specifically with the unnatural L-DNA substrate. The present data imply that the folding of the L- and D-enantiomers of the peptide as well as the DNA substrates are exact mirror images of each other in 3-D structure and biological activity, and generalize the chiral-specific nature of biomolecular interaction.
Negi
Shigeru
S
Faculty of Pharmaceutical Sciences, Doshisha Women's University, Koudo, Kyotanabe-Shi, Japan.
Dhanasekaran
Muthu
M
Hirata
Tsuyoshi
T
Urata
Hidehito
H
Sugiura
Yukio
Y
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D014157:Transcription Factors; D004247:DNA