5W0R

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

Summary for 5W0R

• Entry DOI: 10.2210/pdb5w0r/pdb
• Related: 5W0U 5W0Z
• Descriptor: MBP fused activation-induced cytidine deaminase, ZINC ION, CACODYLATE ION, ... (5 entities in total)
• Functional Keywords: class switch recombination, cytidine deaminase, hydrolase
• Biological source: Escherichia coli O157:H7; More
• Cellular location: Nucleus : Q9GZX7
• Total number of polymer chains: 2
• Total formula weight: 123804.72

Authors

Qiao, Q.,Wang, L.,Wu, H. (deposition date: 2017-05-31, release date: 2017-08-16, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)