Structural bases of unphosphorylated STAT1 association and receptor binding

Mol Cell. 2005 Mar 18;17(6):761-71. doi: 10.1016/j.molcel.2005.02.021.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Crystallization
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Humans
  • Immunoprecipitation
  • Interferon gamma Receptor
  • Monte Carlo Method
  • Mutagenesis, Site-Directed
  • Mutation
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphopeptides / metabolism
  • Phosphorylation
  • Protein Binding
  • Receptors, Interferon / chemistry
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism*
  • STAT1 Transcription Factor
  • Trans-Activators / chemistry*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Ultracentrifugation
  • src Homology Domains

Substances

  • DNA-Binding Proteins
  • Peptide Fragments
  • Phosphopeptides
  • Receptors, Interferon
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators

Associated data

  • PDB/1YVL