# DNA Structure Directed AID Deamination During Immunoglobulin Isotype Switching

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2022 · $379,856

## Abstract

Activation-induced cytidine deaminase (AID) catalyzes cytosine deamination (converting
cytosine to uracil) at immunoglobulin (Ig) variable (V) and switch (S) regions in antigen-
stimulated B cells to initiate somatic hypermutation (SHM) and class switch recombination
(CSR). Recently, highly active monomeric recombinant AID has been generated and its crystal
structure solved. Strikingly, the AID structure shows a bifurcated substrate-binding site; whereas
recombinant AID avidly binds branched DNA structures, it only weakly binds ssDNA, which, until
now, has been considered as the cognate substrate for AID in vivo. This groundbreaking
discovery provides exceptional new insight into a collapsed R-loop model that we proposed
several years ago. This untested model better explains many aspects of CSR. With new tools
that we have developed in recent years, we propose to comprehensively test the hypothesis
that the collapsed R-loop structure is the cognate substrate for AID during CSR.

## Key facts

- **NIH application ID:** 10198651
- **Project number:** 5R01AI139039-04
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Kefei Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $379,856
- **Award type:** 5
- **Project period:** 2018-07-24 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198651

## Citation

> US National Institutes of Health, RePORTER application 10198651, DNA Structure Directed AID Deamination During Immunoglobulin Isotype Switching (5R01AI139039-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10198651. Licensed CC0.

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