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Crystal structure of phosphorylated ETS-1 DNA binding and autoinhibitory domains (276-441)Crystal structure of phosphorylated ETS-1 DNA binding and autoinhibitory domains (276-441)
Structural highlights
FunctionETS1_HUMAN Transcription factor.[1] Publication Abstract from PubMedCooperative assemblies of transcription factors (TFs) on target gene enhancers coordinate cell proliferation, fate specification, and differentiation through precise and complicated transcriptional mechanisms. Chemical modifications, such as phosphorylation, of TFs induced by cell signaling, further modulate the dynamic cooperativity of TFs. In this study, we found that various Ets1-containing TF-DNA complexes respond differently to calcium-induced phosphorylation of Ets1, which is known to inhibit Ets1-DNA binding. Crystallographic analysis of a complex comprising Ets1, Runx1, and CBFbeta at the TCRalpha enhancer, revealed that Ets1 acquires robust binding stability in the Runx1 and DNA-complexed state, via allosteric mechanisms. This allows phosphorylated Ets1 to be retained at the TCRalpha enhancer with Runx1, in contrast to other Ets1 target gene enhancers including mb-1 and stromelysin-1. This study provides a structure-based model for cell signaling-dependent regulation of target genes, mediated via chemical modification of TFs. A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions.,Shiina M, Hamada K, Inoue-Bungo T, Shimamura M, Uchiyama A, Baba S, Sato K, Yamamoto M, Ogata K J Mol Biol. 2014 Jul 29. pii: S0022-2836(14)00368-4. doi:, 10.1016/j.jmb.2014.07.020. PMID:25083921[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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