Activation-induced cytidine deaminase: structure-function relationship as based on the study of mutants.
Activation-induced cytidine deaminase (AID; gene symbol AICDA) is the key molecule required to induce immunoglobulin (Ig) class switch recombination (CSR) and somatic hypermutation (SHM) of the variable regions of Ig genes. Its deficiency causes a form of hyper-IgM (HIGM) syndrome. The study of natural AID mutants associated with HIGM as well as engineered mutants led to the characterization of the active domains of the protein. AID, through its cytidine deaminase activity, induces a targeted DNA lesion as an early step required for both CSR and SHM. Besides its cytidine deaminase activity, AID plays a further essential role in CSR, likely by recruiting CSR-specific cofactors by its C-terminus. A similar binding of SHM-specific cofactors to the N-terminal part is suggested by the functional characteristics of N(ter) AID artificial mutants. These data require confirmation in vivo. Finally, AID acts as a homo-, di-, or multimeric complex. Together, these data strongly suggest that AID, a master molecule for antibody diversification, exerts its activity on CSR not only as a cytidine deaminase enzyme but also as a docking protein, recruiting specific cofactors to a multimeric complex.
Durandy
Anne
A
Institut National de la Santé et de la Recherche Médicale (INSERM), U768, Hôpital Necker-Enfants Malades, Paris, France. durandy@necker.fr
Peron
Sophie
S
Taubenheim
Nadine
N
Fischer
Alain
A
D001483:Base Sequence; D003564:Cytidine Deaminase / Q000235:genetics* / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation / Q000502:physiology*; D011485:Protein Binding; D011995:Recombination, Genetic / Q000502:physiology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D046912:Multiprotein Complexes; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase