Fig. 3. The S1 and S3 alleles disrupt highly conserved amino acids in Drosophila Ccr4. (A) Cartoon showing the domains present in DNOCTURNIN, ANGEL and TWIN/CCR4, as well as S. cerevisiae CCR4. The LRR domains are not present in ANGEL and DNOCTURNIN. Five amino acids, corresponding in Drosophila CCR4 to N199, E243, D412, D486 and H526 have been shown to be essential for catalysis in S. cerevisiae (numbered 1-5) (Chen et al., 2002). (B,C) Black boxes: amino acids identical in all three species. Gray boxes: amino acids identical in two of the three species. Numbers designate the position of amino acids in their primary sequences. (B) Alignment of the leucine-rich repeat regions (LRRs) of CCR4 from Drosophila, humans and S. cerevesiae. S. cerevisiae has five LRRs, humans and Drosophila have half of the first LRR and the second, third and fourth LRRs. Deletions of yeast LRRs 4 and 5 have no effect (Clark et al., 2004). The invariant asparagine at the end of repeat 3 is translated as an isoleucine in the twin^S1 allele. (C) Alignment of a region of the sequence between catalytic amino acids 2 and 3 from A, including the site of the S3 lesion. An isoleucine conserved in humans and Drosophila is translated as a serine in the twin^S3 allele. S. pombe also has an isoleucine at this position (not shown), although S. cerevisiae has a valine.