Structural bases of unphosphorylated STAT1 association and receptor binding.
The crystal structure has been determined at 3.0 A resolution for an unphosphorylated STAT1 (1-683) complexed with a phosphopeptide derived from the alpha chain of interferon gamma (IFNgamma) 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 IFNgamma receptor.
Mao
Xiang
X
Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center , The University of Texas, Houston, Texas 77030, USA.
Ren
Zhiyong
Z
Parker
Gregory N
GN
Sondermann
Holger
H
Pastorello
Michael A
MA
Wang
Wei
W
McMurray
John S
JS
Demeler
Borries
B
Darnell
James E
JE
Chen
Xiaomin
X
D003460:Crystallization; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D047468:Immunoprecipitation; D009010:Monte Carlo Method; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010748:Phosphopeptides / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017471:Receptors, Interferon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014461:Ultracentrifugation; D018909:src Homology Domains; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D010748:Phosphopeptides; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human