4J9K

Human DNA polymerase eta-DNA ternary complex: misincorporation G opposite T after a T at the primer 3' end (TA/G)

4J9K の概要

• エントリーDOI: 10.2210/pdb4j9k/pdb
• 関連するPDBエントリー: 3MR2 4DL2 4DL3 4J9L 4J9M 4J9N 4J9O 4J9P 4J9Q 4J9R 4J9S
• 分子名称: DNA polymerase eta, DNA, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: immunoglobulin, a to g transition, misincorporation, wobble base pair, dna polymerase, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9Y253
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 56903.67

構造登録者

Zhao, Y.,Gregory, M.,Biertumpfel, C.,Hua, Y.,Hanaoka, F.,Yang, W. (登録日: 2013-02-16, 公開日: 2013-05-01, 最終更新日: 2023-09-20)

主引用文献

Zhao, Y.,Gregory, M.T.,Biertumpfel, C.,Hua, Y.J.,Hanaoka, F.,Yang, W.
Mechanism of somatic hypermutation at the WA motif by human DNA polymerase eta.
Proc.Natl.Acad.Sci.USA, 110:8146-8151, 2013

PubMed Abstract: Somatic hypermutation is programmed base substitutions in the variable regions of Ig genes for high-affinity antibody generation. Two motifs, RGYW and WA (R, purine; Y, pyrimidine; W, A or T), have been found to be somatic hypermutation hotspots. Overwhelming evidence suggests that DNA polymerase η (Pol η) is responsible for converting the WA motif to WG by misincorporating dGTP opposite the templating T. To elucidate the molecular mechanism, crystal structures and kinetics of human Pol η substituting dGTP for dATP in four sequence contexts, TA, AA, GA, and CA, have been determined and compared. The T:dGTP wobble base pair is stabilized by Gln-38 and Arg-61, two uniquely conserved residues among Pol η. Weak base paring of the W (T:A or A:T) at the primer end and their distinct interactions with Pol η lead to misincorporation of G in the WA motif. Between two WA motifs, our kinetic and structural data indicate that A-to-G mutation occurs more readily in the TA context than AA. Finally, Pol η can extend the T:G mispair efficiently to complete the mutagenesis.

PubMed: 23630267
DOI: 10.1073/pnas.1303126110

実験手法

X-RAY DIFFRACTION (2.03 Å)