Structural highlights
Function
[V_SV5] Blocks host interferon signaling. Induces the ubiquitination and subsequent proteasome-mediated degradation of host STAT1. Acts as an adapter, linking host DDB1-Cullin 4 to STAT2/STAT1 complex. There is an absolute requirement of STAT2 in STAT1 degradation, as V binds specifically to STAT2. Might act as a chaperone keeping the viral nucleoprotein soluble. Interacts with host IFIH1/MDA5 to block its activity in the transduction pathway which leads to the activation of IFN-beta promoter, thus protecting the virus against cell antiviral state.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase.,Li T, Chen X, Garbutt KC, Zhou P, Zheng N Cell. 2006 Jan 13;124(1):105-17. PMID:16413485[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin Y, Horvath F, Aligo JA, Wilson R, He B. The role of simian virus 5 V protein on viral RNA synthesis. Virology. 2005 Aug 1;338(2):270-80. PMID:15950997 doi:http://dx.doi.org/S0042-6822(05)00287-4
- ↑ Li T, Chen X, Garbutt KC, Zhou P, Zheng N. Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell. 2006 Jan 13;124(1):105-17. PMID:16413485 doi:10.1016/j.cell.2005.10.033
