PDBsum entry 4l18

Transcription/DNA

PDB id: 4l18

Contents

Protein chains

142 a.a.

107 a.a.

DNA/RNA

Ligands

GOL

Waters ×143

PDB id:

4l18

Name:

Transcription/DNA

Title:

Crystal structure of runx1 and ets1 bound to tcr alpha promoter (crystal form 3)

Structure:

Runt-related transcription factor 1. Chain: a, e. Fragment: unp residues 48-214. Synonym: runx1, acute myeloid leukemia 1 protein, core-binding factor subunit alpha-2, cbf-alpha-2, oncogene aml-1, polyomavirus enhancer- binding protein 2 alpha b subunit, pea2-alpha b, pebp2-alpha b, sl3-3 enhancer factor 1 alpha b subunit, sl3/akv core-binding factor alpha b subunit. Engineered: yes.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: runx1, aml1, cbfa2, pebp2ab. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

2.30Å R-factor: 0.231 R-free: 0.280

Authors:

T.H.Tahirov

Key ref:

T.Shrivastava et al. (2014). Structural basis of Ets1 activation by Runx1. Leukemia, 28, 2040-2048. PubMed id: 24646888 DOI: 10.1038/leu.2014.111

Date:

02-Jun-13 Release date: 26-Mar-14

Protein chains

Q03347  (RUNX1_MOUSE) -  Runt-related transcription factor 1 from Mus musculus

Seq: 451 a.a.

Struc: 142 a.a.

Protein chains

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

Seq: 441 a.a.

Struc: 107 a.a.

DNA/RNA chains

G-G-A-A-G-C-C-A-C-A-T-C-C-T-C-T 16 bases

C-A-G-A-G-G-A-T-G-T-G-G-C-T-T-C 16 bases

G-G-A-A-G-C-C-A-C-A-T-C-C-T-C-T 16 bases

C-A-G-A-G-G-A-T-G-T-G-G-C-T-T-C 16 bases

DOI no: 10.1038/leu.2014.111

Leukemia 28:2040-2048 (2014)

PubMed id: 24646888

Structural basis of Ets1 activation by Runx1.

T.Shrivastava, K.Mino, N.D.Babayeva, O.I.Baranovskaya, A.Rizzino, T.H.Tahirov.

ABSTRACT

Runx1 is required for definitive hematopoiesis and is well known for its frequent chromosomal translocations and point mutations in leukemia. Runx1 regulates a variety of genes via Ets1 activation on an Ets1•Runx1 composite DNA sequence. The structural basis of such regulation remains unresolved. To address this problem, we determined the crystal structure of the ternary complex containing Runx11-242 and Ets1296-441 bound to T-cell receptor alpha (TCRα) enhancer DNA. In the crystal, an Ets1-interacting domain of Runx1 is bound to the Ets1 DNA-binding domain and displaced an entire autoinhibitory module of Ets1, revealing a novel mechanism of Ets1 activation. The DNA-binding and transcriptional studies with a variety of structure-guided Runx1 mutants confirmed a critical role of direct Ets1•Runx1 interaction in Ets1 activation. More importantly, the discovered mechanism provides a plausible explanation for how the Ets1•Runx1 interaction effectively activates not only a wild-type Ets1, but also a highly inhibited phosphorylated form of Ets1.