Impact of phosphorylation and phosphorylation-null mutants on the activity and deamination specificity of activation-induced cytidine deaminase.

The Journal of Biological Chemistry
Phuong PhamMyron F Goodman

Abstract

Activation-induced cytidine deaminase (AID) initiates somatic hypermutation and class switch recombination in B cells by deaminating C --> U on transcribed DNA. Here we analyze the role of phosphorylation and phosphorylation-null mutants on the biochemical behavior of AID, including enzyme specific activity, processivity, deamination spectra, deamination motif specificity, and transcription-dependent deamination in the presence and absence of RPA. We show that a small fraction of recombinant human AID expressed in Sf9 insect cells is phosphorylated at previously identified residues Ser(38) and Thr(27) and also at Ser(41) and Ser(43). S43P AID has been identified in a patient with hyper-IgM immunodeficiency syndrome. Ser-substituted phosphorylation-null mutants (S38A, S41A, S43A, and S43P) exhibit wild type (WT) activity on single-stranded DNA. Deamination of transcribed double-stranded DNA is similar for WT and mutant AID and occurs with or without RPA. Although WT and AID mutants catalyze processive deamination favoring canonical WRC hot spot motifs (where W represents A/T and R is A/G), their deamination spectra differ significantly. The differences between the WT and AID mutants appear to be caused by the replacement of Ser ...Continue Reading

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Citations

Nov 17, 2009·Science in China. Series C, Life Sciences·Courtney ProchnowXiaoJiang S Chen
Oct 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Velizar ShivarovTasuku Honjo
May 16, 2009·Proceedings of the National Academy of Sciences of the United States of America·Thomas MacCarthyAviv Bergman
Sep 13, 2008·The Journal of Biological Chemistry·Phuong PhamMyron F Goodman
Oct 8, 2008·The Journal of Experimental Medicine·Kevin M McBrideMichel C Nussenzweig
Apr 22, 2009·The Journal of Experimental Medicine·Hong Ming ShenUrsula Storb
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Nov 22, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Linda ChelicoMyron F Goodman
Dec 8, 2010·Molecular and Cellular Biology·Anna GazumyanKevin M McBride
May 17, 2014·Molecular & Cellular Proteomics : MCP·Antonio PalmeriPier Federico Gherardini
Oct 12, 2012·Environmental and Molecular Mutagenesis·Irina S-R WaisertreigerYouri I Pavlov

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