Artificial zinc finger peptides: creation, DNA recognition, and gene regulation.
Proteins control most biological reactions and the disorder of their expression level causes many diseases. The advent of genomic sequencing and the availability of the complete sequences of several genomes provide new opportunities to study biology and to develop therapeutic strategies through specific modulation of the transcription of target genes. Therefore, regulation of the transcription level by "artificial repressors" is of special importance. Of the DNA-binding motifs that have been manipulated by design or selection, Cys2-His2 zinc finger proteins have demonstrated the greatest potential for manipulation into general and specific transcription factors. Of special interest is the feature that this family of proteins has modular structures and can recognize a diverse set of DNA sequences in a sequence-specific manner. Therefore, zinc finger motifs offer an attractive framework for the design of novel DNA binding proteins, and such a DNA binding protein would be expected to possess a unique binding sequence with high specificity and affinity. Principally, two approaches have been taken to the design of artificial zinc finger proteins. One is a selection strategy via phage display methods to alter the recognition sequence, and another is a structure-based linking strategy to extend the length of a DNA recognition sequence. Such novel zinc finger peptides (or proteins) offer great promise for genome-specific transcription switches in the near future.
Nagaoka
M
M
Institute for Chemical Research, Kyoto University Uji, Japan.
Sugiura
Y
Y
D000595:Amino Acid Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation; D008954:Models, Biological; D008969:Molecular Sequence Data; D019151:Peptide Library; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D019151:Peptide Library; D011993:Recombinant Fusion Proteins; D004247:DNA