3I89

Crystal Structure of DDB1 in Complex with the H-Box Motif of WDR22

3I89 の概要

• エントリーDOI: 10.2210/pdb3i89/pdb
• 関連するPDBエントリー: 2B5M 3I7H 3I7K 3I7L 3I7N 3I7O 3I7P 3I8C 3I8E
• 分子名称: DNA damage-binding protein 1, WD repeat-containing protein 22 (2 entities in total)
• 機能のキーワード: ddb1, wdr22, dcaf5, h-box motif, cytoplasm, dna damage, dna repair, dna-binding, host-virus interaction, nucleus, phosphoprotein, polymorphism, ubl conjugation, ubl conjugation pathway, alternative splicing, wd repeat, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q16531
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 128758.31

構造登録者

Li, T.,Robert, E.I.,Breugel, P.C.V.,Strubin, M.,Zheng, N. (登録日: 2009-07-09, 公開日: 2009-12-08, 最終更新日: 2024-11-27)

主引用文献

Li, T.,Robert, E.I.,van Breugel, P.C.,Strubin, M.,Zheng, N.
A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery.
Nat.Struct.Mol.Biol., 17:105-111, 2010

PubMed Abstract: The cullin 4-DNA-damage-binding protein 1 (CUL4-DDB1) ubiquitin ligase machinery regulates diverse cellular functions and can be subverted by pathogenic viruses. Here we report the crystal structure of DDB1 in complex with a central fragment of hepatitis B virus X protein (HBx), whose DDB1-binding activity is important for viral infection. The structure reveals that HBx binds DDB1 through an alpha-helical motif, which is also found in the unrelated paramyxovirus SV5-V protein despite their sequence divergence. Our structure-based functional analysis suggests that, like SV5-V, HBx captures DDB1 to redirect the ubiquitin ligase activity of the CUL4-DDB1 E3 ligase. We also identify the alpha-helical motif shared by these viral proteins in the cellular substrate-recruiting subunits of the E3 complex, the DDB1-CUL4-associated factors (DCAFs) that are functionally mimicked by the viral hijackers. Together, our studies reveal a common yet promiscuous structural element that is important for the assembly of cellular and virally hijacked CUL4-DDB1 E3 complexes.

PubMed: 19966799
DOI: 10.1038/nsmb.1719

実験手法

X-RAY DIFFRACTION (3 Å)