Examining the Structure of Activation‐Induced Cytidine Deaminase (AID)

Abstract

In order to respond to any foreign antigen that might present itself, B cells must produce antibodies of great variety. Activation‐Induced Cytidine Deaminase (AID) is a protein that plays a critical role in the diversification of antibodies.1 Discovered by T. Honjo et al. in 2000, AID is a protein consisting of 198 amino acids that creates a U:G mismatch by deaminating cytosine to uracil in transcribed Ig DNA2. AID helps in the process of binding site differentiation, known as somatic hypermutation (SHM), and class‐switching, known as CSR (class switch DNA recombination).3 The Governor’s Academy MSOE Center for BioMolecular Modeling SMART team used 3‐D modeling and printing technology to better understand how several aspects of the structure of AID play a critical role in accomplishing the functions of SHM and CSR. Our model highlights Histidine 56, Cysteine 87 and Cysteine 90, which bind zinc ions forming a zinc finger, and the hotspot recognition loop, all of which are involved in DNA binding.4 The catalytic domain, which is similar to the other members of the apolipoprotein B RNA‐editing cytidine deaminase enzymes (APOBEC) is also shown.5 Unfortunately, two of the residues that are most critical for AID functioning could not be shown on our model. Serine 38, which is an important phosphorylation site, was cut out during the isolation and crystallization process and thus is not included in the protein data bank files. Glutamic Acid 58 is the residue most critical for the deamination reaction and was mutated to an Alanine in order to prevent the reaction from occurring so that AID could be isolated with DNA bound.6 Lastly, we highlighted residues R112 and R24. Mutation of either of these Arginines disrupts the configuration of AID, which undermines the ability of AID to undergo SHM and CSR, causing an immunodeficiency disorder called Hyper‐IgM syndrome type 2 (HIGM‐2)