Activation-induced cytidine deaminase splice variants are defective because of the lack of structural support for the catalytic site

The Journal of Immunology : Official Journal of the American Association of Immunologists
Febe van MaldegemCarel J M van Noesel

Abstract

Recently, conflicting results were reported on the hypermutation activity of activation-induced cytidine deaminase (AID) splice variants. With the generation of single point mutations, we studied the structure-function relationship of the amino acids that are commonly absent from all described splice variants. The results from this analysis pointed to several amino acids that are required for class switch recombination (CSR), without perturbing cellular localization or nucleocytoplasmic shuttling. A defect in deaminase activity was found to underlie this CSR deficiency. Interestingly, the most debilitating mutations concentrated on hydrophobic amino acids, suggesting a structural role for this part of the protein. Indeed, by generating homologous amino acid replacements, CSR activity could be restored. These results are in agreement with recent reports on the protein structure of the AID homolog APOBEC3G, suggesting a similar protein composition. In addition, the findings underscore that AID splice variants are unlikely to have preservation of catalytic activity.

References

Mar 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ronda BransteitterMyron F Goodman
Apr 10, 2003·Trends in Genetics : TIG·Joseph E WedekindHarold C Smith
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Satomi ItoTasuku Honjo
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Dec 26, 2006·Nature·Courtney ProchnowXiaojiang S Chen
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Jun 15, 2007·Advances in Immunology·Il-mi OkazakiTasuku Honjo
Jun 15, 2007·Advances in Immunology·Anne DurandyAlain Fischer
Oct 8, 2008·The Journal of Experimental Medicine·Kevin M McBrideMichel C Nussenzweig
Feb 21, 2009·Blood·Febe van MaldegemCarel J M van Noesel
Apr 25, 2009·Journal of Molecular Biology·Elena HarjesHiroshi Matsuo

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Citations

Jul 2, 2020·The Journal of Experimental Medicine·Verónica Delgado-BenitoMichela Di Virgilio
Jun 23, 2015·Oncoscience·Stefan RebhandlRoland Geisberger

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