4h9j | pdb_00004h9j
Crystal structure of N-terminal protease (Npro) of classical swine fever virus.
Structural highlights
FunctionPublication Abstract from PubMedPestiviruses express their genome as a single polypeptide that is subsequently cleaved into individual proteins by host- and virus-encoded proteases. The pestivirus N-terminal protease (N(pro)) is a cysteine autoprotease that cleaves between its own C-terminus and the N-terminus of the core protein. Due to its unique sequence and catalytic site, it forms its own cysteine protease family C53. After self-cleavage, N(pro) is no longer active as a protease. The released N(pro) suppresses the induction of the host's type-I interferon-alpha/beta (IFN-alpha/beta) response. N(pro) binds interferon regulatory factor-3 (IRF3), the key transcriptional activator of IFN-alpha/beta genes, and promotes degradation of IRF3 by the proteasome, thus preventing induction of the IFN-alpha/beta response to pestivirus infection. Here we report the crystal structures of pestivirus N(pro). N(pro) is structurally distinct from other known cysteine proteases and has a novel "clam shell" fold consisting of a protease domain and a zinc-binding domain. The unique fold of N(pro) allows auto-catalysis at its C-terminus and subsequently conceals the cleavage site in the active site of the protease. Although many viruses interfere with type I IFN induction by targeting the IRF3 pathway, little information is available regarding structure or mechanism of action of viral proteins that interact with IRF3. The distribution of amino acids on the surface of N(pro) involved in targeting IRF3 for proteasomal degradation provides insight into the nature of N(pro)'s interaction with IRF3. The structures thus establish the mechanism of auto-catalysis and subsequent auto-inhibition of trans-activity of N(pro), and its role in subversion of host immune response. The Structure of Classical Swine Fever Virus N(pro): A Novel Cysteine Autoprotease and Zinc-Binding Protein Involved in Subversion of Type I Interferon Induction.,Gottipati K, Ruggli N, Gerber M, Tratschin JD, Benning M, Bellamy H, Choi KH PLoS Pathog. 2013 Oct;9(10):e1003704. doi: 10.1371/journal.ppat.1003704. Epub, 2013 Oct 17. PMID:24146623[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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