6UBF

Role of Beta-hairpin motifs in the DNA duplex opening by the Rad4/XPC nucleotide excision repair complex

6UBF の概要

• エントリーDOI: 10.2210/pdb6ubf/pdb
• 分子名称: DNA repair protein RAD4, UV excision repair protein RAD23, DNA (5'-D(*TP*TP*GP*AP*CP*TP*CP*(G47)P*AP*CP*AP*TP*CP*CP*C*GP*CP*TP*AP*CP*AP*A)-3'), ... (4 entities in total)
• 機能のキーワード: dna damage repair, beta hairpin motif, chemical crosslinking, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94412.64

構造登録者

Paul, D.,Min, J.H. (登録日: 2019-09-11, 公開日: 2020-10-14, 最終更新日: 2024-11-06)

主引用文献

Chen, X.,Velmurugu, Y.,Zheng, G.,Park, B.,Shim, Y.,Kim, Y.,Liu, L.,Van Houten, B.,He, C.,Ansari, A.,Min, J.H.
Kinetic gating mechanism of DNA damage recognition by Rad4/XPC.
Nat Commun, 6:5849-, 2015

PubMed Abstract: The xeroderma pigmentosum C (XPC) complex initiates nucleotide excision repair by recognizing DNA lesions before recruiting downstream factors. How XPC detects structurally diverse lesions embedded within normal DNA is unknown. Here we present a crystal structure that captures the yeast XPC orthologue (Rad4) on a single register of undamaged DNA. The structure shows that a disulphide-tethered Rad4 flips out normal nucleotides and adopts a conformation similar to that seen with damaged DNA. Contrary to many DNA repair enzymes that can directly reject non-target sites as structural misfits, our results suggest that Rad4/XPC uses a kinetic gating mechanism whereby lesion selectivity arises from the kinetic competition between DNA opening and the residence time of Rad4/XPC per site. This mechanism is further supported by measurements of Rad4-induced lesion-opening times using temperature-jump perturbation spectroscopy. Kinetic gating may be a general mechanism used by site-specific DNA-binding proteins to minimize time-consuming interrogations of non-target sites.

PubMed: 25562780
DOI: 10.1038/ncomms6849

実験手法

X-RAY DIFFRACTION (4.597 Å)