Variable Control of Ets-1 DNA Binding by Multiple Phosphates in an Unstructured Region

作者：Miles A. Pufall, Gregory Lee, Mary L. Nelson, Hyun-Seo Kang, Algirdas Vėlyvis, Lewis E. Kay, Lawrence P. McIntosh, Barbara J. Graves · 发表于：Science · 年份：2005 · DOI：10.1126/science.1111915 · 被引用次数：255 · 研究领域：RNA Research and Splicing、Protein Structure and Dynamics、Protein Kinase Regulation and GTPase Signaling

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.