PDBsum entry 4ond

Transcription/DNA

PDB id: 4ond

Contents

Protein chains

72 a.a.

DNA/RNA

Metals

_ZN ×8

Waters ×132

PDB id:

4ond

Name:

Transcription/DNA

Title:

Ancestral steroid receptor 2 dbd helix mutant - ere DNA complex

Structure:

Ancestral sr2 helix mutant. Chain: a, b, e, f. Fragment: DNA binding domain. Engineered: yes. Other_details: phylogenetically reconstructed. 5'-d( Cp Cp Ap Gp Gp Tp Cp Ap Gp Ap Gp Tp Gp Ap Cp Cp Tp G) -3'. Chain: i, k. Engineered: yes.

Source:

Synthetic construct. Organism_taxid: 32630. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic: yes

Resolution:

2.25Å R-factor: 0.188 R-free: 0.216

Authors:

E.O.Ortlund,M.N.Murphy

Key ref:

A.N.McKeown et al. (2014). Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module. Cell, 159, 58-68. PubMed id: 25259920 DOI: 10.1016/j.cell.2014.09.003

Date:

28-Jan-14 Release date: 29-Oct-14

Protein chains

No UniProt id for this chain

Struc: 72 a.a.

DNA/RNA chains

C-C-A-G-G-T-C-A-G-A-G-T-G-A-C-C-T-G 18 bases

T-C-A-G-G-T-C-A-C-T-C-T-G-A-C-C-T-G 18 bases

C-C-A-G-G-T-C-A-G-A-G-T-G-A-C-C-T-G 18 bases

T-C-A-G-G-T-C-A-C-T-C-T-G-A-C-C-T-G 18 bases

DOI no: 10.1016/j.cell.2014.09.003

Cell 159:58-68 (2014)

PubMed id: 25259920

Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.

A.N.McKeown, J.T.Bridgham, D.W.Anderson, M.N.Murphy, E.A.Ortlund, J.W.Thornton.

ABSTRACT

Complex gene regulatory networks require transcription factors (TFs) to bind distinct DNA sequences. To understand how novel TF specificity evolves, we combined phylogenetic, biochemical, and biophysical approaches to interrogate how DNA recognition diversified in the steroid hormone receptor (SR) family. After duplication of the ancestral SR, three mutations in one copy radically weakened binding to the ancestral estrogen response element (ERE) and improved binding to a new set of DNA sequences (steroid response elements, SREs). They did so by establishing unfavorable interactions with ERE and abolishing unfavorable interactions with SRE; also required were numerous permissive substitutions, which nonspecifically improved cooperativity and affinity of DNA binding. Our findings indicate that negative determinants of binding play key roles in TFs' DNA selectivity and-with our prior work on the evolution of SR ligand specificity during the same interval-show how a specific new gene regulatory module evolved without interfering with the integrity of the ancestral module.