Title | Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Li T, Chen X, Garbutt KC, Zhou P, Zheng N |
Journal | Cell |
Volume | 124 |
Issue | 1 |
Pagination | 105-17 |
Date Published | 2006 Jan 13 |
ISSN | 0092-8674 |
Keywords | Crystallization, Crystallography, X-Ray, Cullin Proteins, DNA-Binding Proteins, Genes, Viral, Humans, Models, Molecular, Mutagenesis, Site-Directed, Protein Conformation, Protein Structure, Tertiary, Ubiquitin-Protein Ligases, Viral Structural Proteins |
Abstract | The DDB1-Cul4A ubiquitin ligase complex promotes protein ubiquitination in diverse cellular functions and is reprogrammed by the V proteins of paramyxoviruses to degrade STATs and block interferon signaling. Here we report the crystal structures of DDB1 alone and in complex with the simian virus 5 V protein. The DDB1 structure reveals an intertwined three-propeller cluster, which contains two tightly coupled beta propellers with a large pocket in between and a third beta propeller flexibly attached on the side. The rigid double-propeller fold of DDB1 is targeted by the viral V protein, which inserts an entire helix into the double-propeller pocket, whereas the third propeller domain docks DDB1 to the N terminus of the Cul4A scaffold. Together, these results not only provide structural insights into how the virus hijacks the DDB1-Cul4A ubiquitin ligase but also establish a structural framework for understanding the multiple functions of DDB1 in the uniquely assembled cullin-RING E3 machinery. |
DOI | 10.1016/j.cell.2005.10.033 |
Alternate Journal | Cell |
PubMed ID | 16413485 |
Grant List | CA098210 / CA / NCI NIH HHS / United States CA107134 / CA / NCI NIH HHS / United States |
Related Lab:
Related Faculty:
Pengbo Zhou, Ph.D.