6J44

Crystal structure of the redefined DNA-binding domain of human XPA

6J44 の概要

• エントリーDOI: 10.2210/pdb6j44/pdb
• 分子名称: DNA repair protein complementing XP-A cells, ZINC ION (3 entities in total)
• 機能のキーワード: dna repair, nucleotide excision repair, scaffold protein, zinc finger, dna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17538.58

構造登録者

Lian, F.M.,Yang, X.,Yang, W.,Jiang, Y.L.,Qian, C. (登録日: 2019-01-07, 公開日: 2019-05-29, 最終更新日: 2024-03-27)

主引用文献

Lian, F.M.,Yang, X.,Yang, W.,Jiang, Y.L.,Qian, C.
Structural characterization of the redefined DNA-binding domain of human XPA.
Biochem.Biophys.Res.Commun., 514:985-990, 2019

PubMed Abstract: XPA (xeroderma pigmentosum complementation group A), a key scaffold protein in nucleotide excision repair (NER) pathway, is important in DNA damage verification and repair proteins recruitment. Earlier studies had mapped the minimal DNA-binding domain (MBD) of XPA to a region corresponding to residues 98-219. However, recent studies indicated that the region involving residues 98-239 is the redefined DNA-binding domain (DBD), which binds to DNA substrates with a much higher binding affinity than MBD and possesses a nearly identical binding affinity to the full-length XPA protein. However, the structure of the redefined DBD domain of XPA (XPA-DBD) remains to be investigated. Here, we present the crystal structure of XPA-DBD at 2.06 Å resolution. Structure of the C-terminal region of XPA has been extended by 21 residues (Arg211-Arg231) as compared with previously reported MBD structures. The structure reveals that the C-terminal extension (Arg211-Arg231) is folded as an α-helix with multiple basic residues. The positively charged surface formed in the last C-terminal helix suggests its critical role in DNA binding. Further structural analysis demonstrates that the last C-terminal region (Asp217-Thr239) of XPA-DBD might undergo a conformational change to directly bind to the DNA substrates. This study provides a structural basis for understanding the possible mechanism of enhanced DNA-binding affinity of XPA-DBD.

PubMed: 31092331
DOI: 10.1016/j.bbrc.2019.05.050

実験手法

X-RAY DIFFRACTION (2.06 Å)