DNA Structure Directed AID Deamination During Immunoglobulin Isotype Switching

活化诱导的胞苷脱氨酶（AID）催化胞嘧啶脱氨（转化为胞嘧啶脱氨）。 胞嘧啶至尿嘧啶）在抗原中的免疫球蛋白（IG）可变（V）和转换（S）区， 刺激B细胞启动体细胞超突变（SHM）和类别转换重组 （CSR）。最近，已经产生了高活性的单体重组AID，并且其晶体 结构解决。引人注目的是，AID结构显示出分叉的底物结合位点;而 重组AID强烈地结合分支DNA结构，它仅微弱地结合ssDNA，直到 现在，已被认为是体内AID的同源底物。这项开创性 这一发现为我们提出的折叠R环模型提供了新的见解， 几年前这个未经检验的模型更好地解释了企业社会责任的许多方面。使用新工具 近年来，我们已经开发，我们建议全面测试的假设 折叠的R环结构是CSR期间AID的同源底物。

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.