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Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region

TitleVariable control of Ets-1 DNA binding by multiple phosphates in an unstructured region
Publication TypeJournal Article
Year of Publication2005
AuthorsPufall, MA, Lee, GM, Nelson, ML, Kang, HS, Velyvis, A, Kay, LE, McIntosh, LP, Graves, BJ
JournalScience
Volume309
Pagination142-145
Date PublishedJul
Type of ArticleArticle
ISBN Number0036-8075
Keywordsallosteric regulation, AUTOINHIBITION, DOMAIN, DYNAMICS, NMR-SPECTROSCOPY, PHOSPHORYLATION, PROTEIN, SITES, TRANSACTIVATION, TRANSCRIPTION FACTOR NFAT1
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.

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