Simian virus 5 V protien complexed with human DDB1
Simian virus 5 / Homo sapiens (human)
A polyubiquitin chain acts as a tag for protein degradation, and Ubiquitine-dependent proteolysis is well-used mechanism for eukaryotes to modulate protein activities negatively. Three enzymes participate in protein ubiquitination, and at the last step, the ubiquitin-protein E3 ligases catalyze ubiquitin transfer from a ubiquitin-conjugating enzyme (E2) to the substrate. Ubiquitin ligase E3 is a multisubunit protein complex. A prototype E3 consists of a RING finger protein that recognizes E2 enzyme, scaffold protein called cullin protein, cullin adoptor protein and F-box protein which recognizes and recruits the target. Unlike other cullin protein, Cul4A binds to DDB1 that shares no sequence homology with any cullin adaptor. DDB1 is an evolutionarily conserved protein from fission yeast to humans. DDB1 is a core subunit of the cul4A-based ubiquitin ligase complex, and has been proposed to either dock a substrate to the E3 enzyme or indirectly recruit a substrate through additional adaptors. Recent studies have shown that various pathogenic viruses are able to hijack ubiquitin-dependent proteolysis to degrade host proteins important for host’s survival. For example, a V protein produced by simian virus 5 (SV5) can bind DDB1 directly to promote rapid degradation of the STAT proteins, the key signal transducers in the antiviral response pathway.
The structure shown here is a complex of human DDB1 and the simian virus 5V protein (SV5-V). DDB1 consists of three seven-bladed beta propellers (BPA, BPB, BPC) and a C-terminal helical domain (CTD) to form an intertwined three-propeller cluster. The SV5-V is composed of one alpha helix and two long loops, and a central seven-stranded beta sheet sandwiched by them. The SV5-V inserts its N-terminal helix into the BPA-BPC pocket of DDB1. The authors of this paper suggest that the surface of the SV5-V core domain is a potential protein interaction site and directly bind STAT protein, and recruit STATs to E3 enzyme.
Protein Data Bank (PDB)
author: Miho Higurashi