Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited

Regan M.C.; Horanyi P.S.; Pryor Jr. E.E.Sarver J.L.Cafiso D.S.Bushweller J.H.

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Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited

机译：Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited

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The Ets-Related Gene (ERG) belongs to the Ets family of transcription factors and is critically important for maintenance of the hematopoietic stem cell population. A chromosomal translocation observed in the majority of human prostate cancers leads to the aberrant overexpression of ERG. We have identified regions flanking the ERG Ets domain responsible for autoinhibition of DNA binding and solved crystal structures of uninhibited, autoinhibited, and DNA-bound ERG. NMR-based measurements of backbone dynamics show that uninhibited ERG undergoes substantial dynamics on the millisecond-to-microsecond timescale but autoinhibited and DNA-bound ERG do not. We propose a mechanism whereby the allosteric basis of ERG autoinhibition is mediated predominantly by the regulation of Ets-domain dynamics with only modest structural changes.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第33期|13374-13379|共6页
作者
Regan M.C.; Horanyi P.S.; Pryor Jr. E.E.Sarver J.L.Cafiso D.S.Bushweller J.H.;
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作者单位

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, United States;

Department of Chemistry, University of Virginia, Charlottesville, VA 22904, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种英语
中图分类自然科学总论;
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Structural; dynamic studies; allosterically autoinhibited;

Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited

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