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Title

A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery

Authors
Li, Ti
Strubin, M.
Zheng, N.
Published in Nature Structural & Molecular Biology. 2010, vol. 17, no. 1, p. 105-111
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.
Keywords Blotting, WesternColony-Forming Units AssayCrystallizationCullin Proteins/*metabolismDNA-Binding Proteins/*chemistry/*metabolismGreen Fluorescent ProteinsHeLa CellsHumansImmunoprecipitationLuciferases*Models, MolecularProtein Binding*Protein Structure, SecondaryTrans-Activators/*chemistry/metabolismTwo-Hybrid System TechniquesUbiquitin-Protein Ligases/metabolism
Identifiers
PMID: 19966799
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Structures
Research group Régulation de l'expression des gènes du virus de l'hépatite B (294)
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(ISO format)
LI, Ti et al. A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. In: Nature Structural & Molecular Biology, 2010, vol. 17, n° 1, p. 105-111. https://archive-ouverte.unige.ch/unige:20645

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Deposited on : 2012-05-22

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