3EI2

Structure of hsDDB1-drDDB2 bound to a 16 bp abasic site containing DNA-duplex

3EI2 の概要

• エントリーDOI: 10.2210/pdb3ei2/pdb
• 関連するPDBエントリー: 3EI1 3EI3 3EI4
• 分子名称: DNA damage-binding protein 1, DNA damage-binding protein 2, 5'-D(*DAP*DAP*DAP*DTP*DGP*DAP*DAP*DTP*(3DR)P*DAP*DAP*DGP*DCP*DAP*DGP*DG)-3', ... (6 entities in total)
• 機能のキーワード: uv-damage, ddb, nucleotide excision repair, xeroderma pigmentosum, alternative splicing, disease mutation, dna damage, dna repair, dna-binding, nucleus, phosphoprotein, polymorphism, wd repeat, ubl conjugation pathway, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm: Q16531; Nucleus (By similarity): Q2YDS1
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 182667.55

構造登録者

Scrima, A.,Thoma, N.H. (登録日: 2008-09-15, 公開日: 2009-01-20, 最終更新日: 2024-03-20)

主引用文献

Scrima, A.,Konickova, R.,Czyzewski, B.K.,Kawasaki, Y.,Jeffrey, P.D.,Groisman, R.,Nakatani, Y.,Iwai, S.,Pavletich, N.P.,Thoma, N.H.
Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.
Cell(Cambridge,Mass.), 135:1213-1223, 2008

PubMed Abstract: Ultraviolet (UV) light-induced pyrimidine photodimers are repaired by the nucleotide excision repair pathway. Photolesions have biophysical parameters closely resembling undamaged DNA, impeding discovery through damage surveillance proteins. The DDB1-DDB2 complex serves in the initial detection of UV lesions in vivo. Here we present the structures of the DDB1-DDB2 complex alone and bound to DNA containing either a 6-4 pyrimidine-pyrimidone photodimer (6-4PP) lesion or an abasic site. The structure shows that the lesion is held exclusively by the WD40 domain of DDB2. A DDB2 hairpin inserts into the minor groove, extrudes the photodimer into a binding pocket, and kinks the duplex by approximately 40 degrees. The tightly localized probing of the photolesions, combined with proofreading in the photodimer pocket, enables DDB2 to detect lesions refractory to detection by other damage surveillance proteins. The structure provides insights into damage recognition in chromatin and suggests a mechanism by which the DDB1-associated CUL4 ubiquitin ligase targets proteins surrounding the site of damage.

PubMed: 19109893
DOI: 10.1016/j.cell.2008.10.045

実験手法

X-RAY DIFFRACTION (2.6 Å)