Variable Control of Ets-1 DNA Binding by Multiple Phosphates in an Unstructured Region
- 1 July 2005
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 309 (5731) , 142-145
- https://doi.org/10.1126/science.1111915
Abstract
Cell signaling that culminates in posttranslational modifications directs protein activity. Here we report how multiple Ca2+-dependent phosphorylation sites within the transcription activator Ets-1 act additively to produce graded DNA binding affinity. Nuclear magnetic resonance spectroscopic analyses show that phosphorylation shifts Ets-1 from a dynamic conformation poised to bind DNA to a well-folded inhibited state. These phosphates lie in an unstructured flexible region that functions as the allosteric effector of autoinhibition. Variable phosphorylation thus serves as a “rheostat” for cell signaling to fine-tune transcription at the level of DNA binding.Keywords
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