2NNY

Crystal structure of the Ets1 dimer DNA complex.

Summary for 2NNY

• Entry DOI: 10.2210/pdb2nny/pdb
• Related: 1GVJ 1K78
• Descriptor: 5'-D(*T*AP*GP*AP*CP*AP*GP*GP*AP*AP*GP*CP*AP*CP*TP*TP*CP*CP*TP*GP*GP*AP*G)-3', 5'-D(*A*CP*TP*CP*CP*AP*GP*GP*AP*AP*GP*TP*GP*CP*TP*TP*CP*CP*TP*GP*TP*CP*T)-3', C-ets-1 protein, ... (4 entities in total)
• Functional Keywords: ets-1, protein-dna complex, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P14921
• Total number of polymer chains: 4
• Total formula weight: 53879.06

Authors

Lamber, E.P.,Kachalova, G.S.,Wilmanns, M. (deposition date: 2006-10-24, release date: 2008-03-04, Last modification date: 2023-08-30)

Primary citation

Lamber, E.P.,Vanhille, L.,Textor, L.C.,Kachalova, G.S.,Sieweke, M.H.,Wilmanns, M.
Regulation of the transcription factor Ets-1 by DNA-mediated homo-dimerization.
Embo J., 27:2006-2017, 2008

PubMed Abstract: The function of the Ets-1 transcription factor is regulated by two regions that flank its DNA-binding domain. A previously established mechanism for auto-inhibition of monomeric Ets-1 on DNA response elements with a single ETS-binding site, however, has not been observed for the stromelysin-1 promoter containing two palindromic ETS-binding sites. We present the structure of Ets-1 on this promoter element, revealing a ternary complex in which protein homo-dimerization is mediated by the specific arrangement of the two ETS-binding sites. In this complex, the N-terminal-flanking region is required for ternary protein-DNA assembly. Ets-1 variants, in which residues from this region are mutated, loose the ability for DNA-mediated dimerization and stromelysin-1 promoter transactivation. Thus, our data unravel the molecular basis for relief of auto-inhibition and the ability of Ets-1 to function as a facultative dimeric transcription factor on this site. Our findings may also explain previous data of Ets-1 function in the context of heterologous transcription factors, thus providing a molecular model that could also be valid for Ets-1 regulation by hetero-oligomeric assembly.

PubMed: 18566588
DOI: 10.1038/emboj.2008.117

Experimental method

X-RAY DIFFRACTION (2.58 Å)