The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds - PubMed (original) (raw)

Fig. 6

Sequence alignment of PWWP-containing proteins. a, The residues ‘WP’ (magenta) are conserved among all, except for the BR140 family in which a Tyr in the place of Trp. Other conserved residues are highlighted with a yellow background (hydrophobic), blue (basic) and red (acidic). The accession numbers are colored based on the range of calculated pI value: blue (8–10) and magenta (6–7). The prefix M indicates mouse; H, human; At, A. thaliana; and Sp, Schizosaccharomyces pombe. In addition to the sequences shown, the other PWWP-containing proteins used in alignment are from human (AAD53063, AAD32631, CAC28351, AAF25871, CAB75688, BAA86439, BAA86600, NP_055392, CAB66669, AAG44637); mouse (AAD33084, AF064553, AAB88445, BAA90478, BAA22896, AAF65469, BAA22895); A. thaliana (AAF64539, AAF23297, CAB86049, BAB11589, AAF29390, AAD24842, CAB93724, CAB87752, AAF18621, BAA97320, CAB71104); zebrafish (BG307263, AW305577, AAC40177, AI588565), Drosophila (AAF56762, AAF59276, AAF57004, AAF55003, AAF57177, AAF58494), Xenopus (AW636253); Saccharomyces. cerevisiae (AAB64719, NP_013758); S. pombe (CAA22121, AB027814); bovine (CAA40348); Onchocerca volvulus (BE132518); Ceanorhabditis elegans (AAB52437); and Triticum aestivum (BE500209). b, The schematic representation of PWWP-containing proteins. Abbreviations are NLS (nuclear localization signal), HMG (high mobility group), PCNA (PCNA binding motif), SET (Suvar39, Enhancer of zeste, Trithorax), bromo (bromodomain) and chromo (chromodomain). WHSC1 is a 136-kDa protein expressed ubiquitously in early development and preferentially in rapidly growing embryonic tissues. BS69 is a 69-kDa nuclear protein that specifically suppresses adenovirus E1A-activated transcription. BR140 shows similarity to a group of transcriptional coactivators, including the TAF250 subunit of TFIID. MSH6 is mammalian MutS homolog essential for DNA mismatch repair, which contains a PWWP domain at its extreme N-terminus. However, msh6 orthologs in S. cerevisiae, C. elegans and A. thaliana do not contain this domain. The fully sequenced C. elegans contains only one PWWP protein, AAB52437; this protein contains an N-terminal PWWP domain and a C-terminal SIR2-like domain. Although the known eukaryotic members of the NAD-dependent protein deacetylase SIR2 family often contains the N- and/or C-terminal extensions outside of a conserved core region, none of these contains a PWWP domain. A CXXC zinc-binding motif is found in the structure of an Archaeoglobus fulgidus SIR2 homolog, which contains a CXXC-X15–20-CXXC zinc-binding sequence motif.