Combinatorial targeting of ribbon-helix-helix artificial transcription factors to chimeric recognition sites.

ABSTRACT: Artificial transcription factors (ATFs) are potent synthetic biology tools for modulating endogenous gene expression and precision genome editing. The ribbon-helix-helix (RHH) superfamily of transcription factors are widespread in bacteria and archaea. The principal DNA binding determinant in this family comprises a two-stranded antiparallel β-sheet (ribbons) in which a pair of eight-residue motifs insert into the major groove. Here, we demonstrate that ribbons of divergent RHH proteins are compact and portable elements that can be grafted into a common α-helical scaffold producing active ATFs. Hybrid proteins cooperatively recognize DNA sites possessing core tetramer boxes whose functional spacing is dictated by interactions between the α-helical backbones. These interactions also promote

SUBMITTER: Zampini M 

PROVIDER: S-EPMC3413123 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature