National Center for
2AQF: Structural and functional analysis of ADA2 alpha swirm domain
Nat. Struct. Mol. Biol. (2005) 12 p.1078-1085
The evolutionarily conserved Swi3p, Rsc8p and Moira (SWIRM) domain is found in many chromosomal proteins involved in chromatin modifications or remodeling. Here we report the three-dimensional solution structure of the SWIRM domain from the human transcriptional adaptor ADA2alpha. The structure reveals a five-helix bundle consisting of two helix-turn-helix motifs connected by a central long helix, reminiscent of the histone fold. Using structural and biochemical analyses, we showed that the SWIRM domains of human ADA2alpha and SMARC2 bind to double-stranded and nucleosomal DNA, and we identified amino acid residues required for this function. We demonstrated that the ADA2alpha SWIRM domain is colocalized with lysine-acetylated histone H3 in the cell nucleus and that it potentiates the ACF remodeling activity by enhancing accessibility of nucleosomal linker DNA bound to histone H1. These data suggest a functional role of the SWIRM domain in chromatin remodeling.