Structure of an activated Dictyostelium STAT in its DNA-unbound form.
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.
Soler-Lopez
Montserrat
M
European Molecular Biology Laboratory, Grenoble Outstation, B.P. 181, 38042 Grenoble Cedex 9, France.
Petosa
Carlo
C
Fukuzawa
Masashi
M
Ravelli
Raimond
R
Williams
Jeffrey G
JG
Müller
Christoph W
CW
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D019281:Dimerization; D019143:Evolution, Molecular; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014867:Water / Q000737:chemistry; D018909:src Homology Domains / Q000235:genetics
D010748:Phosphopeptides; D015800:Protozoan Proteins; D014867:Water; D004247:DNA