title: Cation-pi/H-bond stair motifs at protein-DNA interfaces.
abstract: H-bonds and cation-pi interactions between nucleic acid bases and amino acid side-chains are known to occur often concomitantly at the interface between protein and double-stranded DNA. Here we define and analyze stair-shaped motifs, which simultaneously involve base stacking, H-bond and cation-pi interactions. They consist of two successive bases along the DNA stack, one in cation-pi interaction with an amino acid side-chain that carries a total or partial positive charge, and the other H-bonded with the same side-chain. A survey of 52 high-resolution structures of protein/DNA complexes reveals the occurrence of such motifs in the majority of the complexes, the most frequent of these motifs involving Arg side-chains and G bases. These stair motifs are sometimes part of larger motifs, called multiple stair motifs, which contain several successive stairs; zinc finger proteins for example exhibit up to quadruple stairs. In another kind of stair motif extension, termed cation-pi chain motif, an amino acid side-chain or a nucleic acid base forms simultaneously two cation-pi interactions. Such a motif is observed in several homeodomains, where it involves a DNA base in cation-pi interactions with an Arg in the minor groove and an Asn in the major groove. A different cation-pi chain motif contains an Arg in cation-pi with a G and a Tyr, and is found in ets transcription factors. Still another chain motif is encountered in proteins that expulse a base from the DNA stack and replace it by an amino acid side-chain carrying a net or partial positive charge, which forms cation-pi interactions with the two neighboring bases along the DNA strand. The striking conservation of typical stair and cation-pi chain motifs within families of protein/DNA complexes suggests that they might play a structural and/or functional role and might moreover influence electron migration through the DNA double helix.
authors.affiliation: Ingénierie Biomoléculaire - CP 165/64, Université Libre de Bruxelles, 50 avenue Roosevelt, B-1050 Bruxelles, Belgium. mrooman@ulb.ac.be
authors.forename: Marianne
authors.initials: M
authors.lastname: Rooman
authors.forename: Jacky
authors.initials: J
authors.lastname: Liévin
authors.forename: Eric
authors.initials: E
authors.lastname: Buisine
authors.forename: René
authors.initials: R
authors.lastname: Wintjens
mesh_terms: D001120:Arginine / Q000737:chemistry; D020029:Base Pairing; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006147:Guanine / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011506:Proteins; D006147:Guanine; D004247:DNA; D001120:Arginine