Recognition rules for binding of Zn-Cys2His2 transcription factors to operator DNA.
The molecules of Zn-finger transcription factors consist of several similar small protein units. We analyzed the crystal structures 46 basic units of 22 complexes of Zn-Cys2His2 family with the fragments of operator DNA. We showed that the recognition of DNA occurs via five protein contacts. The canonical binding positions of the recognizing α-helix were -1, 3, 6, and 7, which make contacts with the tetra-nucleotide sequence ZXYZ of the coding DNA strand; here the canonical binding triplet is underlined. The non-coding DNA strand forms only one contact at α-helix position 2. We have discovered that there is a single highly conservative contact His7α with the phosphate group of nucleotide Z, which precedes each triplet XYZ of the coding DNA chain. This particular contact is invariant for the all Zn-Cys2His2 family with high frequency of occurrence 83%, which we considered as an invariant recognition rule. We have also selected a previously unreported Zn-Cys2His2-Arg subfamily of 21 Zn-finger units bound with DNA triplets, which make two invariant contacts with residues Arg6α and His7α with the coding DNA chain. These contacts show frequency of occurrence 100 and 90%, and are invariant recognition rule. Three other variable protein-DNA contacts are formed mainly with the bases and specify the recognition patterns of individual factor units. The revealed recognition rules are inherent for the Zn-Cys2His2 family and Zn-Cys2His2-Arg subfamily of different taxonomic groups and can distinguish members of these families from any other family of transcription factors.
a Institute of Theoretical Experimental Biophysics, Russian Academy of Sciences , Pushchino 142290 , Moscow Region , Russia.
R V
RV
Polozov
V S
VS
Sivozhelezov
Yu N
YN
Chirgadze
V V
VV
Ivanov
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009875:Operator Regions, Genetic; D011485:Protein Binding; D017433:Protein Structure, Secondary; D014157:Transcription Factors / Q000737:chemistry*; D016335:Zinc Fingers
D014157:Transcription Factors
DNA binding protein family; Zn-finger; invariant contacts; protein-DNA recognition; recognition rules; transcription factor; variable contacts