5JJ4

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

5JJ4 の概要

• エントリーDOI: 10.2210/pdb5jj4/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900010
• 分子名称: 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)
• 機能のキーワード: aid mbp-fuison deaminase, hydrolase
• 由来する生物種: Escherichia coli O157:H7; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 186707.15

構造登録者

Pedersen, L.C.,Goodman, M.F.,Pham, P.,Afif, S.A. (登録日: 2016-04-22, 公開日: 2016-06-29, 最終更新日: 2023-09-27)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.807 Å)