DOI: 10.1002/pro.5560050214. Structural coupling of the inhibitory regions flanking the ETS domain of murine Ets‐1

Structural coupling of the inhibitory regions flanking the ETS domain of murine Ets‐1

10.1002/pro.5560050214

Crossref journal-article

Wiley

Protein Science (311)

Abstract

AbstractSeveral members of the ets gene family of transcription factors show negative regulation of DNA binding by intramolecular interactions. A structural mechanism for this auto‐inhibition is investigated using a 161‐residue N‐terminal deletion mutant of murine Ets‐1, Ets‐1ΔN280. This protein shows a similar reduced affinity for DNA as native Ets‐1 because it contains the ETS domain in context of the flanking amino‐ and carboxy‐terminal regions that together mediate repression of DNA binding. The secondary structure of Ets‐1ΔN280 was determined using NMR chemical shift, NOE, J coupling, and amide hydrogen exchange information. In addition to the winged helix‐turn‐helix ETS domain, Ets‐1ΔN280 contains two α‐helices in the amino‐terminal inhibitory region and one α‐helix in the carboxy‐terminal inhibitory region. Chemical shift comparisons were made between this protein and an activated form of Ets‐1 lacking the amino‐terminal inhibitory region. The spectral differences demonstrate that the amino‐ and carboxy‐terminal inhibitory sequences are structurally coupled to one another, thus explaining the observation that both regions are required for the repression of DNA binding. Furthermore, these data show that the inhibitory sequences also interact directly with the first helix of the intervening ETS domain, thereby providing a pathway for the repression of DNA binding. These results lead to a model of an inhibitory module in Ets‐1 composed of both the amino‐ and carboxy‐terminal regions interfaced with the ETS domain. This establishes the structural framework for understanding the intramolecular inhibition of Ets‐1 DNA binding.

Bibliography

Donaldson, L. W., Mcintosh, L. P., Skalicky, J. J., Petersen, J. M., & Graves, B. J. (1996). Structural coupling of the inhibitory regions flanking the ETS domain of murine Etsâ1. Protein Science, 5(2), 296â309. Portico.

Authors 5

Logan W. Donaldson (first)
Lawrence P. Mcintosh (additional)
Jack J. Skalicky (additional)
Jeannine M. Petersen (additional)
Barbara J. Graves (additional)

References 66 Referenced 54

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Dates

Type	When
Created	15 years, 1 month ago (July 12, 2010, 5:31 a.m.)
Deposited	1 year, 10 months ago (Oct. 26, 2023, 12:03 p.m.)
Indexed	1 month, 2 weeks ago (July 19, 2025, 11:59 p.m.)
Issued	29 years, 7 months ago (Feb. 1, 1996)
Published	29 years, 7 months ago (Feb. 1, 1996)
Published Online	16 years, 8 months ago (Dec. 31, 2008)
Published Print	29 years, 7 months ago (Feb. 1, 1996)

Funders 0

None

BibTeX

@article{Donaldson_1996, title={Structural coupling of the inhibitory regions flanking the ETS domain of murine Ets‐1}, volume={5}, ISSN={1469-896X}, url={http://dx.doi.org/10.1002/pro.5560050214}, DOI={10.1002/pro.5560050214}, number={2}, journal={Protein Science}, publisher={Wiley}, author={Donaldson, Logan W. and Mcintosh, Lawrence P. and Skalicky, Jack J. and Petersen, Jeannine M. and Graves, Barbara J.}, year={1996}, month=feb, pages={296–309} }

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