PDBsum entry 3wts

Transcription/DNA

PDB id: 3wts

Contents

Protein chains

119 a.a.

130 a.a.

118 a.a.

101 a.a.

DNA/RNA

Waters ×87

PDB id:

3wts

Name:

Transcription/DNA

Title:

Crystal structure of the complex comprised of ets1, runx1, cbfbeta, and the tcralpha gene enhancer DNA

Structure:

Runt-related transcription factor 1. Chain: a, f. Fragment: unp residues 60-263. Synonym: 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: aml1, cbfa2, pebp2ab, runx1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: cbfb, pebp2b, pebpb2. Homo sapiens. Human.

Resolution:

2.35Å R-factor: 0.249 R-free: 0.279

Authors:

M.Shiina,K.Hamada,K.Ogata

Key ref:

M.Shiina et al. (2015). A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions. J Mol Biol, 427, 1655-1669. PubMed id: 25083921 DOI: 10.1016/j.jmb.2014.07.020

Date:

21-Apr-14 Release date: 13-Aug-14

Protein chains

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

Seq: 451 a.a.

Struc: 119 a.a.*

Protein chains

Q08024  (PEBB_MOUSE) -  Core-binding factor subunit beta from Mus musculus

Seq: 187 a.a.

Struc: 130 a.a.

Protein chain

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

Seq: 441 a.a.

Struc: 118 a.a.

Protein chain

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

Seq: 441 a.a.

Struc: 101 a.a.

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

DNA/RNA chains

G-A-A-G-C-C-A-C-A-T-C-C-T-C-T 15 bases

A-G-A-G-G-A-T-G-T-G-G-C-T-T-C 15 bases

G-A-A-G-C-C-A-C-A-T-C-C-T-C-T 15 bases

A-G-A-G-G-A-T-G-T-G-G-C-T-T-C 15 bases

DOI no: 10.1016/j.jmb.2014.07.020

J Mol Biol 427:1655-1669 (2015)

PubMed id: 25083921

A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions.

M.Shiina, K.Hamada, T.Inoue-Bungo, M.Shimamura, A.Uchiyama, S.Baba, K.Sato, M.Yamamoto, K.Ogata.

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.