A structural basis for the biochemical behavior of activation-induced deoxycytidine deaminase class-switch recombination-defective hyper-IgM-2 mutants.

ABSTRACT: Hyper-IgM syndrome type 2 stems from mutations in activation-induced deoxycytidine deaminase (AID) that abolish immunoglobulin class-switch recombination, causing an accumulation of IgM and absence of IgG, IgA, and IgE isotypes. Although hyper-IgM syndrome type 2 is rare, the 23 missense mutations identified in humans span almost the entire gene for AID resulting in a recessive phenotype. Using high resolution x-ray structures for Apo3G-CD2 as a surrogate for AID, we identify three classes of missense mutants as follows: catalysis (class I), substrate interaction (class II), and structural integrity (class III). Each mutant was expressed and purified from insect cells and compared biochemically to wild type (WT) AID. Four point mutants retained catalytic activity at 1/3rd to 1/200th the le

SUBMITTER: Mu Y 

PROVIDER: S-EPMC3431652 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature