3WWT

Crystal Structure of the Y3:STAT1ND complex

Summary for 3WWT

• Entry DOI: 10.2210/pdb3wwt/pdb
• Descriptor: Signal transducer and activator of transcription 1-alpha/beta, C' protein, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: alpha protein, interferon inhibition, signal transduction, transcriptional activation, transcription-viral protein complex, transcription/viral protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 31752.18

Authors

Oda, K.,Sakaguchi, T.,Matoba, Y. (deposition date: 2014-06-27, release date: 2015-07-01, Last modification date: 2023-11-08)

Primary citation

Oda, K.,Matoba, Y.,Irie, T.,Kawabata, R.,Fukushi, M.,Sugiyama, M.,Sakaguchi, T.
Structural Basis of the Inhibition of STAT1 Activity by Sendai Virus C Protein.
J.Virol., 89:11487-11499, 2015

PubMed Abstract: Sendai virus (SeV) C protein inhibits the signal transduction pathways of interferon alpha/beta (IFN-α/β) and IFN-γ by binding to the N-terminal domain of STAT1 (STAT1ND), thereby allowing SeV to escape from host innate immunity. Here we determined the crystal structure of STAT1ND associated with the C-terminal half of the C protein (Y3 [amino acids 99 to 204]) at a resolution of 2.0 Å. This showed that two molecules of Y3 symmetrically bind to each niche created between two molecules of the STAT1ND dimer. Molecular modeling suggested that an antiparallel form of the full-length STAT1 dimer can bind only one Y3 molecule and that a parallel form can bind two Y3 molecules. Affinity analysis demonstrated anticooperative binding of two Y3 molecules with the STAT1 dimer, which is consistent with the hypothetical model that the second Y3 molecule can only target the STAT1 dimer in a parallel form. STAT1 with excess amounts of Y3 was prone to inhibit the dephosphorylation at Tyr(701) by a phosphatase. In an electrophoretic mobility shift assay, tyrosine-phosphorylated STAT1 (pY-STAT1) with Y3 associated with the γ-activated sequence, probably as high-molecular-weight complexes (HMWCs), which may account for partial inhibition of a reporter assay from IFN-γ by Y3. Our study suggests that the full-length C protein interferes with the domain arrangement of the STAT1 dimer, leading to the accumulation of pY-STAT1 and the formation of HMWCs. In addition, we discuss the mechanism by which phosphorylation of STAT2 is inhibited in the presence of the C protein after stimulation by IFN-α/β.

PubMed: 26339056
DOI: 10.1128/JVI.01887-15

Experimental method

X-RAY DIFFRACTION (2 Å)