5A39

Structure of Rad14 in complex with cisplatin containing DNA

5A39 の概要

• エントリーDOI: 10.2210/pdb5a39/pdb
• 分子名称: DNA REPAIR PROTEIN RAD14, DNA, 5'-D(*DTP*GP*AP*TP*GP*AP*CP*CP*GP*TP*AP*GP*AP)-3', ... (6 entities in total)
• 機能のキーワード: replication, dna repair, dna damage recognition, cisplatin
• 由来する生物種: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST); 詳細
• 細胞内の位置: Nucleus: P28519
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 53830.51

構造登録者

Koch, S.C.,Kuper, J.,Gasteiger, K.L.,Wichlein, N.,Strasser, R.,Eisen, D.,Geiger, S.,Schneider, S.,Kisker, C.,Carell, T. (登録日: 2015-05-28, 公開日: 2015-06-24, 最終更新日: 2024-05-08)

主引用文献

Koch, S.C.,Kuper, J.,Gasteiger, K.L.,Simon, N.,Strasser, R.,Eisen, D.,Geiger, S.,Schneider, S.,Kisker, C.,Carell, T.
Structural Insights Into the Recognition of Cisplatin and Aaf-Dg Lesion by Rad14 (Xpa).
Proc.Natl.Acad.Sci.USA, 112:8272-, 2015

PubMed Abstract: Nucleotide excision repair (NER) is responsible for the removal of a large variety of structurally diverse DNA lesions. Mutations of the involved proteins cause the xeroderma pigmentosum (XP) cancer predisposition syndrome. Although the general mechanism of the NER process is well studied, the function of the XPA protein, which is of central importance for successful NER, has remained enigmatic. It is known, that XPA binds kinked DNA structures and that it interacts also with DNA duplexes containing certain lesions, but the mechanism of interactions is unknown. Here we present two crystal structures of the DNA binding domain (DBD) of the yeast XPA homolog Rad14 bound to DNA with either a cisplatin lesion (1,2-GG) or an acetylaminofluorene adduct (AAF-dG). In the structures, we see that two Rad14 molecules bind to the duplex, which induces DNA melting of the duplex remote from the lesion. Each monomer interrogates the duplex with a β-hairpin, which creates a 13mer duplex recognition motif additionally characterized by a sharp 70° DNA kink at the position of the lesion. Although the 1,2-GG lesion stabilizes the kink due to the covalent fixation of the crosslinked dG bases at a 90° angle, the AAF-dG fully intercalates into the duplex to stabilize the kinked structure.

PubMed: 26100901
DOI: 10.1073/PNAS.1508509112

実験手法

X-RAY DIFFRACTION (2.8 Å)