Structure of an activated Dictyostelium STAT in its DNA-unbound form

Mol Cell. 2004 Mar 26;13(6):791-804. doi: 10.1016/s1097-2765(04)00130-3.


Dd-STATa is a STAT protein which transcriptionally regulates cellular differentiation in Dictyostelium discoideum, the only non-metazoan known to employ SH2 domain signaling. The 2.7 A crystal structure of a tyrosine phosphorylated Dd-STATa homodimer reveals a four-domain architecture similar to that of mammalian STATs 1 and 3, but with an inverted orientation for the coiled-coil domain. Dimerization is mediated by SH2 domain:phosphopeptide interactions and by a direct interaction between SH2 domains. The unliganded Dd-STATa dimer adopts a fully extended conformation remarkably different from that of the DNA-bound mammalian STATs, implying a large conformational change upon target site recognition. Buried hydrophilic residues predicted to destabilize the coiled-coil domain suggest how hydrophobic residues may become exposed and mediate nuclear export. Functional and evolutionary implications for metazoan STAT proteins are discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Nucleus / metabolism
  • Conserved Sequence
  • Crystallography, X-Ray
  • DNA / genetics
  • DNA / metabolism*
  • Dictyostelium / genetics
  • Dictyostelium / growth & development
  • Dictyostelium / metabolism*
  • Dimerization
  • Evolution, Molecular
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphopeptides / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Water / chemistry
  • src Homology Domains / genetics


  • Phosphopeptides
  • Protozoan Proteins
  • Water
  • DNA

Associated data

  • PDB/1UUR
  • PDB/1UUS