SWIRM domain of chromosomal DNA binding protein ADA2α
Eucaryotic DNA forms, together with proteins called histon, a densely packed structure called chromatin. Thus, the chromatin structure must be first disassembled when DNA transcription starts. This process is called "chromatin remodeling".There are two distinct chromatin remodeling mechanisms; one uses ATP dependent hydrolysis, and another uses histon modification such as phosphorylation and methylation to disrupt or alter the DNA-histon binding. Most chromatin modifying factors are multiprotein complexes consisting of both enzymatic and non-enzymatic subunits. The structural motifs of non-catalytic subunit in the chromatin modifying complexes are conserved among various organisms. One of such motifs is Swi3p, Rsc8p and Moira(SWIRM) domain that binds to DNA and dinucleosome.
The protein described here is SWIRM domain of human chromosomal DNA binding protein ADA2α(355-443 residues). ADA2α SWIRM domain forms “winged helix” that is built on a central long helix(α3) connecting two helix-turn-helix motifs at the N-(α1-turn-α2) and C termini(α4-turn-α5) of the protein(fig1). In the winged helix of SWIRM domain, the surface exposed cationic amino acid residues on α5 helix(Lys426, Arg428, Arg436 and Arg442) are important for DNA binding. Because winged helix is observed in the other DNA binding proteins such as histons(H1, H2B and H5) and nucleosome binding protein E2F4, SWIRM domain would bind to DNA with an orientation similar to those proteins(fig2). SWIRM domain binds to not only DNA but also to nucleosome especially dinucleosome. Dinucleosome binding of SWIRM domain remodels internucleosomal DNA and results in transcription activation.
fig1. Winged helix of ADA2α SWIRM domain.α1-α2 helix-turn-helix, α3 helix and α4-α5 helix-turn-helix are colored red, green and blue respectively.
fig2. ADA2α SWIRM domain(left) and nucleosome binding protein E2F4-DNA complex(right: 1CF7). The colors of ADA2α SWIRM domain correspond to those in fig1.
Protein Data Bank (PDB)
Qian, C. Zhang, Q. Li, S.D. Zeng, L. Walsh, M.J. Zhou, M.-M.; "Structure and chromosomal DNA binding of the SWIRM domain"; Nat.Struct.Mol.Biol.; (2005) 12:1078-1085 PubMed:16299514.
author: Daisuke Ino