Structural studies of Ets-1/Pax5 complex formation on DNA.
Pax5 regulates the B cell-specific expression of the mb-1 gene together with members of the Ets family of transcriptional activators. The Ets proteins on their own bind poorly to the Pax5/Ets binding site, but can be recruited to the site by cooperative interactions with Pax5. The structure of the ETS domain of Ets-1 and the paired domain of Pax5 bound to DNA reveals the molecular details of the selective recruitment of different Ets proteins by Pax5. Comparison with structures of Ets-1 alone bound to both high- and low-affinity DNA sites reveals that Pax5 alters the Ets-1 contacts with DNA. The ability of one protein to alter the DNA sequence-specific contacts of another provides a general mechanism for combinatorial regulation of transcription.
Garvie
C W
CW
Department of Biophysics and Biophysical Chemistry, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Hagman
J
J
Wolberger
C
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D051757:PAX5 Transcription Factor; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051757:PAX5 Transcription Factor; D010446:Peptide Fragments; D011506:Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D004247:DNA