The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBEC-1.
Activation-induced deaminase (AID) uses base deamination for class-switch recombination and somatic hypermutation and is related to the mammalian RNA-editing enzyme apolipoprotein B editing catalytic subunit 1 (APOBEC-1). CDD1 is a yeast ortholog of APOBEC-1 that exhibits cytidine deaminase and RNA-editing activity. Here, we present the crystal structure of CDD1 at 2.0-A resolution and its use in comparative modeling of APOBEC-1 and AID. The models explain dimerization and the need for trans-acting loops that contribute to active site formation. Substrate selectivity appears to be regulated by a central active site "flap" whose size and flexibility accommodate large substrates in contrast to deaminases of pyrimidine metabolism that bind only small nucleosides or free bases. Most importantly, the results suggested both AID and APOBEC-1 are equally likely to bind single-stranded DNA or RNA, which has implications for the identification of natural AID targets.
Xie
Kefang
K
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Sowden
Mark P
MP
Dance
Geoffrey S C
GS
Torelli
Andrew T
AT
Smith
Harold C
HC
Wedekind
Joseph E
JE
D000071479:APOBEC-1 Deaminase; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003564:Cytidine Deaminase / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017393:RNA Editing; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D013577:Syndrome; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007075:Immunoglobulin M; D029701:Saccharomyces cerevisiae Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C487509:CDD1 protein, S cerevisiae; D003564:Cytidine Deaminase