Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase.
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.
Li
Ti
T
Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
Chen
Xiujuan
X
Garbutt
Kenneth C
KC
Zhou
Pengbo
P
Zheng
Ning
N
D003460:Crystallization; D018360:Crystallography, X-Ray; D044842:Cullin Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D005814:Genes, Viral; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015678:Viral Structural Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
C114234:CUL4A protein, human; D044842:Cullin Proteins; C091435:DDB1 protein, human; D004268:DNA-Binding Proteins; C097019:V protein, Simian parainfluenza virus 5; D015678:Viral Structural Proteins; D044767:Ubiquitin-Protein Ligases