7NUF

Vaccinia virus protein 018 in complex with STAT1

Summary for 7NUF

• Entry DOI: 10.2210/pdb7nuf/pdb
• Descriptor: Signal transducer and activator of transcription 1-alpha/beta, Uncharacterized protein 18, SULFATE ION, ... (5 entities in total)
• Functional Keywords: transcription factor, inhibitor, complex, viral, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 65790.41

Authors

Pantelejevs, T.,Talbot-Cooper, C.,Smith, G.L.,Hyvonen, M. (deposition date: 2021-03-12, release date: 2021-07-28, Last modification date: 2024-02-07)

Primary citation

Talbot-Cooper, C.,Pantelejevs, T.,Shannon, J.P.,Cherry, C.R.,Au, M.T.,Hyvonen, M.,Hickman, H.D.,Smith, G.L.
Poxviruses and paramyxoviruses use a conserved mechanism of STAT1 antagonism to inhibit interferon signaling.
Cell Host Microbe, 30:357-372.e11, 2022

PubMed Abstract: The induction of interferon (IFN)-stimulated genes by STATs is a critical host defense mechanism against virus infection. Here, we report that a highly expressed poxvirus protein, 018, inhibits IFN-induced signaling by binding to the SH2 domain of STAT1, thereby preventing the association of STAT1 with an activated IFN receptor. Despite encoding other inhibitors of IFN-induced signaling, a poxvirus mutant lacking 018 was attenuated in mice. The 2.0 Å crystal structure of the 018:STAT1 complex reveals a phosphotyrosine-independent mode of 018 binding to the SH2 domain of STAT1. Moreover, the STAT1-binding motif of 018 shows similarity to the STAT1-binding proteins from Nipah virus, which, similar to 018, block the association of STAT1 with an IFN receptor. Overall, these results uncover a conserved mechanism of STAT1 antagonism that is employed independently by distinct virus families.

PubMed: 35182467
DOI: 10.1016/j.chom.2022.01.014

Experimental method

X-RAY DIFFRACTION (2.00040159011 Å)