3WTZ

Crystal structure of ETS-1 DNA binding and autoinhibitory domains (276-441)

Summary for 3WTZ

• Entry DOI: 10.2210/pdb3wtz/pdb
• Related: 3WTS 3WTT 3WTU 3WTV 3WTW 3WTX 3WTY 3WU0 3WU1
• Descriptor: Protein C-ets-1 (2 entities in total)
• Functional Keywords: transcription, ets-1, autoinhibition, ets domain, dna-binding, isopeptide bond, nucleus, phosphoprotein, proto-oncogene, transcription regulation
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P14921
• Total number of polymer chains: 2
• Total formula weight: 38433.46

Authors

Shiina, M.,Hamada, K.,Ogata, K. (deposition date: 2014-04-21, release date: 2014-08-20, Last modification date: 2023-11-08)

Primary citation

Shiina, M.,Hamada, K.,Inoue-Bungo, T.,Shimamura, M.,Uchiyama, A.,Baba, S.,Sato, K.,Yamamoto, M.,Ogata, K.
A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions.
J.Mol.Biol., 427:1655-1669, 2015

PubMed Abstract: Cooperative 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 CBFβ at the TCRα 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 TCRα 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.

PubMed: 25083921
DOI: 10.1016/j.jmb.2014.07.020

Experimental method

X-RAY DIFFRACTION (2.61 Å)