Structural bases of unphosphorylated STAT1 association and receptor binding

Xiang Mao, Zhiyong Ren, Gregory N. Parker, Holger Sondermann, Michael A. Pastorello, Wei Wang, John S. McMurray, Borries Demeler, James E. Darnell, Xiaomin Chen

Research output: Contribution to journalArticlepeer-review

234 Scopus citations


The crystal structure has been determined at 3.0 Å resolution for an unphosphorylated STAT1 (1-683) complexed with a phosphopeptide derived from the α chain of interferon γ (IFNγ) receptor. Two dimer interfaces are seen, one between the N domains (NDs) (amino acid residues 1-123) and the other between the core fragments (CFs) (residues 132-683). Analyses of the wild-type (wt) and mutant STAT1 proteins by static light scattering, analytical ultracentrifugation, and coimmunoprecipitation suggest that STAT1 is predominantly dimeric prior to activation, and the dimer is mediated by the ND interactions. The connecting region between the ND and the CF is flexible and allows two interconvertable orientations of the CFs, termed " antiparallel" or "parallel," as determined by SH2 domain orientations. Functional implications of these dimer conformations are discussed. Also revealed in this structure is the detailed interaction between STAT1 SH2 domain and its docking site on IFNγ receptor.

Original languageEnglish
Pages (from-to)761-771
Number of pages11
JournalMolecular Cell
Issue number6
StatePublished - Mar 18 2005


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