4OLN

Ancestral Steroid Receptor 1 in complex with estrogen response element DNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

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

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

(2014) Cell 159: 58-68

  • DOI: https://doi.org/10.1016/j.cell.2014.09.003
  • Primary Citation of Related Structures:  
    4OLN, 4OND, 4OOR, 4OV7

  • PubMed 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.


  • Organizational Affiliation

    Institute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AncSR1
A, B
82synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
5'-D(*CP*CP*AP*GP*GP*TP*CP*AP*GP*AP*GP*TP*GP*AP*CP*CP*TP*GP*A)-3'C [auth E]19N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
5'-D(*TP*CP*AP*GP*GP*TP*CP*AP*CP*TP*CP*TP*GP*AP*CP*CP*TP*GP*G)-3'D [auth F]19N/A
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.176 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.184α = 90
b = 36.425β = 121.63
c = 90.939γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
SERGUIdata collection
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-29
    Type: Initial release
  • Version 1.1: 2017-11-22
    Changes: Refinement description
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations