A reinterpretation of the dimerization interface of the N-terminal domains of STATs.
The crystal structures of the N-terminal domain (N-domain) and the core region of the STAT family of transcription factors have been determined previously. STATs can form cooperative higher order structures (tetramers or higher oligomers) while bound to DNA. The crystal packing in the STAT4 N-domain crystal structure, determined at 1.5 A resolution, suggests two alternate organizations of the N-domain dimer. We now present the results of site directed mutagenesis of residues predicted to be involved at each dimer interface. Our results indicate that the dimer interface suggested earlier as being physiologically relevant is, in fact, unlikely to be so. Given the alternative model for the N-domain dimer, the ability of the N-domain to mediate interactions of two STAT dimers on DNA remains unchanged.
Chen
Xiaomin
X
Department of Biochemistry and Molecular Biology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Bhandari
Rashna
R
Vinkemeier
Uwe
U
Van Den Akker
Focco
F
Darnell
James E
JE
Kuriyan
John
J
D001665:Binding Sites; D002942:Circular Dichroism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D050797:STAT4 Transcription Factor; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014461:Ultracentrifugation
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators