AID is one of the ancestral members of the AID/APOBEC family of cytidine deaminases and it is highly conserved from cartilaginous fish to humans (Conticello et al., 2005; Zhao et al, 2005). SHM developed before CSR, but AID's ability to catalyze CSR developed before the CSR reaction itself (Barreto et al., 2005a; Ichikawa et al., 2006; Wakae et al., 2006). On the basis of modeling by threading and comparative computational models that rely on the crystal structure of a yeast cytidine deaminase, AID is believed to be organized in an N-terminal catalytic domain spanning roughly the first 150 residues whose fold may resemble that of yeast and E. coli cytidine deaminase catalytic domains, and a C-terminal pseudocatalytic domain of more uncertain structure (Xie et al., 2004; Zaim and Kierzek, 2003). Numerous inactivating AID mutations have been found in HIGM2 patients affecting both the catalytic and the pseudocatalytic domains, implying a strong structural constraint in the molecule (Quartier et al., 2004; Revy et al., 2000).
Similarly to other cytidine deaminases AID forms dimers and/or multimers when overexpressed in 293T cells (Ta et al., 2003). A careful analysis of deletion and point mutants showed that AID forms homodimers in the absence of DNA or other cofactors, and mapped the region responsible for dimerization between residues 27 and 56 (Wang et al., 2006a). Functional analysis of mutants in this region showed that dimer formation is required for efficient CSR (Wang et al, 2006a).
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