@article {541,
	title = {Inhibitory module of Ets-1 allosterically regulates DNA binding through a dipole-facilitated phosphate contact},
	journal = {Journal of Biological Chemistry},
	volume = {277},
	number = {3},
	year = {2002},
	note = {ISI Document Delivery No.: 514CWTimes Cited: 21Cited Reference Count: 50},
	month = {Jan},
	pages = {2225-2233},
	type = {Article},
	abstract = {DNA binding of the transcription factor Ets-1 is negatively regulated by three inhibitory helices that lie near the ETS domain. The current model suggests that this negative regulation, termed autoinhibition, is caused by the energetic expense of a DNA-induced structural transition that includes the unfolding of one inhibitory helix. This report investigates the role of helix H1 of the ETS domain in the autoinhibition mechanism. Previous structural studies modeled the inhibitory helices packing together and connecting with helix H1, suggesting a role of this helix in the configuration of an inhibitory module. Recently, high-resolution structures of the ETS domain-DNA interface indicate that the N terminus of helix H1 directly contacts DNA. The contact, which is augmented by the macrodipole of helix H1, consists of a hydrogen bond between the amide NH of leucine 337 in helix HI and the oxygen of a corresponding phosphate. We propose that this hydrogen bond positions helix H1 to be a link between autoinhibition and DNA binding. Four independent approaches tested this hypothesis. First, the hydrogen bond was disrupted by removal of the phosphate in a missing phosphate analysis. Second, base pairs that surround the helix HI-contacting phosphate and appear to dictate DNA backbone conformation were mutated. Next, a hydrophobic residue in helix H1 that is expected to position the N terminus of the helix was altered. Finally, a residue on the surface of helix 111 that may contact the inhibitory elements was changed. In each case DNA binding and autoinhibition was affected. Taken together, the results demonstrate the role of the dipole-facilitated phosphate contact in DNA binding. Furthermore, the findings support a model in which helix H1 links the inhibitory elements to the ETS domain. We speculate that this helix, which is conserved in all Ets proteins, provides a common route to regulation.},
	keywords = {ALPHA-HELIX, AUTO-INHIBITION, COMPLEX, DOMAIN, FACTORS ELK-1, INDIRECT READOUT, MURINE ETS-1, PROTEINS, RECOGNITION, TRANSCRIPTION FACTOR},
	isbn = {0021-9258},
	url = {<Go to ISI>://000173421300083},
	author = {Wang, H. and McIntosh, L. P. and Graves, B. J.}
}
@article {4696,
	title = {The highly conserved beta-hairpin of the paired DNA-binding domain is required for assembly of Pax-Ets ternary complexes},
	journal = {Molecular and Cellular Biology},
	volume = {19},
	number = {3},
	year = {1999},
	note = {ISI Document Delivery No.: 168MYTimes Cited: 37Cited Reference Count: 57},
	month = {Mar},
	pages = {2231-2241},
	type = {Article},
	abstract = {Pax family transcription factors bind DNA through the paired domain. This domain, which is comprised of two helix-turn-helix motifs and a beta-hairpin structure, is a target of mutations in congenital disorders of mice and humans. Previously, we showed that Pax-5 (B-cell-specific activator protein) recruits proteins of the Ets proto-oncogene family to bind a composite DNA site that is essential for efficient transcription of the early-B-cell-specific mb-1 promoter. Here, evidence is provided for specific interactions between Ets-1 and the amino-terminal subdomains of Pax proteins. By tethering deletion fragments of Pax-5 to a heterologous DNA-binding domain, we show that 73 amino acids (amino acids 12 to 84) of its amino-terminal subdomain can recruit the ETS domain of Ets-1 to bind the composite site. Furthermore, an amino acid (Gln22) within the highly conserved beta-hairpin motif of Pax-5 is essential for efficient recruitment of Ets-1. The ability to recruit Ets proteins to bind DNA is a shared property of Pax proteins, as demonstrated by cooperative DNA binding of Ets-1 with sequences derived from the paired domains of Pax-2 and Pax-3. The strict conservation of sequences required for recruitment of Ets proteins suggests that Pax-Ets interactions are important for regulating transcription in diverse tissues during cellular differentiation.},
	keywords = {B-CELL-DEVELOPMENT, BOX, GENE, HMG DOMAIN, MURINE ETS-1, POINT MUTATION, STRUCTURAL BASIS, TRANSCRIPTION FACTORS, V-ETS, WAARDENBURG-SYNDROME},
	isbn = {0270-7306},
	url = {<Go to ISI>://000078697900061},
	author = {Wheat, W. and Fitzsimmons, D. and Lennox, H. and Krautkramer, S. R. and Gentile, L. N. and McIntosh, L. P. and Hagman, J.}
}
