PDBsum entry 2nny

Transcription/DNA

PDB id: 2nny

Contents

Protein chains

129 a.a. *

DNA/RNA

Waters ×46

* Residue conservation analysis

PDB id:

2nny

Name:

Transcription/DNA

Title:

Crystal structure of the ets1 dimer DNA complex.

Structure:

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'. Chain: c. Engineered: yes. 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'. Chain: d. Engineered: yes. C-ets-1 protein.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: ets1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.58Å R-factor: 0.235 R-free: 0.271

Authors:

E.P.Lamber,G.S.Kachalova,M.Wilmanns

Key ref:

E.P.Lamber et al. (2008). Regulation of the transcription factor Ets-1 by DNA-mediated homo-dimerization. Embo J, 27, 2006-2017. PubMed id: 18566588 DOI: 10.1038/emboj.2008.117

Date:

24-Oct-06 Release date: 04-Mar-08

Protein chains

P14921  (ETS1_HUMAN) -  Protein C-ets-1 from Homo sapiens

Seq: 441 a.a.

Struc: 129 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DNA/RNA chains

A-G-A-C-A-G-G-A-A-G-C-A-C-T-T-C-C-T-G-G-A-G 22 bases

C-T-C-C-A-G-G-A-A-G-T-G-C-T-T-C-C-T-G-T-C-T 22 bases

DOI no: 10.1038/emboj.2008.117

Embo J 27:2006-2017 (2008)

PubMed id: 18566588

Regulation of the transcription factor Ets-1 by DNA-mediated homo-dimerization.

E.P.Lamber, L.Vanhille, L.C.Textor, G.S.Kachalova, M.H.Sieweke, M.Wilmanns.

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.