5W1C

Crystal structure of MBP fused activation-induced cytidine deaminase (AID) in complex with cytidine

5W1C の概要

• エントリーDOI: 10.2210/pdb5w1c/pdb
• 分子名称: MBP fused activation-induced cytidine deaminase, DNA (5'-D(*GP*TP*TP*CP*AP*AP*GP*GP*CP*CP*AP*G)-3'), DNA (5'-D(*CP*TP*GP*GP*CP*CP*TP*TP*GP*AP*AP*C)-3'), ... (7 entities in total)
• 機能のキーワード: class switch recombination, cytidine deaminase, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Escherichia coli O157:H7; 詳細
• 細胞内の位置: Nucleus : Q9GZX7
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132185.78

構造登録者

Qiao, Q.,Wang, L.,Wu, H. (登録日: 2017-06-02, 公開日: 2017-08-16, 最終更新日: 2023-10-04)

主引用文献

Qiao, Q.,Wang, L.,Meng, F.L.,Hwang, J.K.,Alt, F.W.,Wu, H.
AID Recognizes Structured DNA for Class Switch Recombination.
Mol. Cell, 67:361-373.e4, 2017

PubMed Abstract: Activation-induced cytidine deaminase (AID) initiates both class switch recombination (CSR) and somatic hypermutation (SHM) in antibody diversification. Mechanisms of AID targeting and catalysis remain elusive despite its critical immunological roles and off-target effects in tumorigenesis. Here, we produced active human AID and revealed its preferred recognition and deamination of structured substrates. G-quadruplex (G4)-containing substrates mimicking the mammalian immunoglobulin switch regions are particularly good AID substrates in vitro. By solving crystal structures of maltose binding protein (MBP)-fused AID alone and in complex with deoxycytidine monophosphate, we surprisingly identify a bifurcated substrate-binding surface that explains structured substrate recognition by capturing two adjacent single-stranded overhangs simultaneously. Moreover, G4 substrates induce cooperative AID oligomerization. Structure-based mutations that disrupt bifurcated substrate recognition or oligomerization both compromise CSR in splenic B cells. Collectively, our data implicate intrinsic preference of AID for structured substrates and uncover the importance of G4 recognition and oligomerization of AID in CSR.

PubMed: 28757211
DOI: 10.1016/j.molcel.2017.06.034

実験手法

X-RAY DIFFRACTION (3.18 Å)