Abstract
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 language | English |
|---|---|
| Pages (from-to) | 761-771 |
| Number of pages | 11 |
| Journal | Molecular Cell |
| Volume | 17 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 18 2005 |
Funding
We thank Drs. G. Zhang, J. Marcotrigiano, D. Jeruzalmi, Y. Jiang, and X. Mu for helpful discussions and/or critically reading the manuscript. Crystal structure of the unphosphorylated STAT1 CF was determined while X.C. was in the laboratory of Dr. John Kuriyan at The Rockefeller University. We are grateful to the staff at ALS beamlines 8.3.1 and 8.2.2 and CHESS beamlines F1 and F2 for export technical support. This work is supported by grants from the Robert A. Welch Foundation, National Institutes of Health (X.C.), and National Science Foundation (B.D.).