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From Proteopedia
Crystal Structure of a Variant Human Activation-induced Deoxycytidine Deaminase as an MBP fusion protein
Structural highlights
DiseaseAICDA_HUMAN Hyper-IgM syndrome type 2. The disease is caused by mutations affecting the gene represented in this entry. FunctionAICDA_HUMAN Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses (PubMed:18722174, PubMed:21385873, PubMed:21518874, PubMed:27716525). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894).[1] [2] [3] [4] [5] MALE_ECO57 Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides (By similarity). Publication Abstract from PubMedActivation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) and class-switch recombination (CSR) by deaminating C-->U during transcription of Ig-variable (V) and Ig-switch (S) region DNA, which is essential to produce high-affinity antibodies. Here we report the crystal structure of a soluble human AID variant at 2.8A resolution that favors targeting WRC motifs (W=A/T, R=A/G) in vitro, and executes Ig V SHM in Ramos B-cells. A specificity loop extending away from the active site to accommodate two purine bases next to C, differs significantly in sequence, length, and conformation from APOBEC proteins Apo3A and Apo3G, which strongly favor pyrimidines at -1 and -2 positions. Individual amino acid contributions to specificity and processivity were measured in relation to a proposed ssDNA binding cleft. This study provides a structural basis for residue contributions to DNA scanning properties unique to AID, and for disease mutations in human HIGM-2 syndrome. Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification.,Pham P, Afif SA, Shimoda M, Maeda K, Sakaguchi N, Pedersen LC, Goodman MF DNA Repair (Amst). 2016 Jul;43:48-56. doi: 10.1016/j.dnarep.2016.05.029. Epub, 2016 May 13. PMID:27258794[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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