Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 16, Issue 7, Pages 769-U97Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1623
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Funding
- Medical Research Council [MC_U105178806] Funding Source: Medline
- MRC [MC_U105178806] Funding Source: UKRI
- Medical Research Council [MC_U105178806] Funding Source: researchfish
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DNA deaminases underpin pathways in antibody diversification (AID) and anti-viral immunity (APOBEC3s). Here we show how a high-throughput bacterial papillation assay can be used to screen for AID mutants with increased catalytic activity. The upmutations focus on a small number of residues, some highlighting regions implicated in AID's substrate interaction. Many of the upmutations bring the sequence of AID closer to that of APOBEC3s. AID upmutants can yield increased antibody diversification, raising the possibility that modification of AID's specific activity might be used to regulate antibody diversification in vivo. However, upmutation of AID also led to an increased frequency of chromosomal translocations, suggesting that AID's specific activity may have been limited by the risk of genomic instability.
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