5JJ4

Crystal Structure of a Variant Human Activation-induced Deoxycytidine Deaminase as an MBP fusion protein

Summary for 5JJ4

• Entry DOI: 10.2210/pdb5jj4/pdb
• Related PRD ID: PRD_900010
• Descriptor: Maltose-binding periplasmic protein,Single-stranded DNA cytosine deaminase, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, ZINC ION, ... (5 entities in total)
• Functional Keywords: aid mbp-fuison deaminase, hydrolase
• Biological source: Escherichia coli O157:H7; More
• Total number of polymer chains: 3
• Total formula weight: 186707.15

Authors

Pedersen, L.C.,Goodman, M.F.,Pham, P.,Afif, S.A. (deposition date: 2016-04-22, release date: 2016-06-29, Last modification date: 2023-09-27)

Primary citation

Pham, P.,Afif, S.A.,Shimoda, M.,Maeda, K.,Sakaguchi, N.,Pedersen, L.C.,Goodman, M.F.
Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification.
DNA Repair (Amst.), 43:48-56, 2016

PubMed Abstract: Activation-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 2.8Å 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.

PubMed: 27258794
DOI: 10.1016/j.dnarep.2016.05.029

Experimental method

X-RAY DIFFRACTION (2.807 Å)