title: An expanded binding model for Cys2His2 zinc finger protein-DNA interfaces.
abstract: Cys(2)His(2) zinc finger (C2H2-ZF) proteins comprise the largest class of eukaryotic transcription factors. The 'canonical model' for C2H2-ZF protein-DNA interaction consists of only four amino acid-nucleotide contacts per zinc finger domain, and this model has been the basis for several efforts for computationally predicting and experimentally designing protein-DNA interfaces. Here, we perform a systematic analysis of structural and experimental binding data and find that, in addition to the canonical contacts, several other amino acid and base pair combinations frequently play a role in C2H2-ZF protein-DNA binding. We suggest an expansion of the canonical C2H2-ZF model to include one to three additional contacts, and show that computational approaches including these additional contacts improve predictions of DNA targets of zinc finger proteins.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ, USA.
authors.forename: Anton V
authors.initials: AV
authors.lastname: Persikov
authors.forename: Mona
authors.initials: M
authors.lastname: Singh
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D004247:DNA