Toward rules relating zinc finger protein sequences and DNA binding site preferences.
Zinc finger proteins of the Cys2-His2 type consist of tandem arrays of domains, where each domain appears to contact three adjacent base pairs of DNA through three key residues. We have designed and prepared a series of variants of the central zinc finger within the DNA binding domain of Sp1 by using information from an analysis of a large data base of zinc finger protein sequences. Through systematic variations at two of the three contact positions (underlined), relatively specific recognition of sequences of the form 5'-GGGGN(G or T)GGG-3' has been achieved. These results provide the basis for rules that may develop into a code that will allow the design of zinc finger proteins with preselected DNA site specificity.
Desjarlais
J R
JR
Thomas C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 20218.
Berg
J M
JM
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014644:Genetic Variation; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D016329:Sp1 Transcription Factor / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
D015342:DNA Probes; D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D004247:DNA