5HEB

The third PDZ domain from the synaptic protein PSD-95 in complex with a C-terminal peptide derived from CRIPT


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.169 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Origins of Allostery and Evolvability in Proteins: A Case Study.

Raman, A.S.White, K.I.Ranganathan, R.

(2016) Cell 166: 468-480

  • DOI: https://doi.org/10.1016/j.cell.2016.05.047
  • Primary Citation of Related Structures:  
    5HEB, 5HED, 5HET, 5HEY, 5HF1, 5HFB, 5HFC, 5HFF

  • PubMed Abstract: 

    Proteins display the capacity for adaptation to new functions, a property critical for evolvability. But what structural principles underlie the capacity for adaptation? Here, we show that adaptation to a physiologically distinct class of ligand specificity in a PSD95, DLG1, ZO-1 (PDZ) domain preferentially occurs through class-bridging intermediate mutations located distant from the ligand-binding site. These mutations provide a functional link between ligand classes and demonstrate the principle of "conditional neutrality" in mediating evolutionary adaptation. Structures show that class-bridging mutations work allosterically to open up conformational plasticity at the active site, permitting novel functions while retaining existing function. More generally, the class-bridging phenotype arises from mutations in an evolutionarily conserved network of coevolving amino acids in the PDZ family (the sector) that connects the active site to distant surface sites. These findings introduce the concept that allostery in proteins could have its origins not in protein function but in the capacity to adapt.


  • Organizational Affiliation

    Green Center for Systems Biology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Disks large homolog 4119Rattus norvegicusMutation(s): 0 
Gene Names: Dlg4Dlgh4Psd95
UniProt
Find proteins for P31016 (Rattus norvegicus)
Explore P31016 
Go to UniProtKB:  P31016
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP31016
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Cysteine-rich PDZ-binding protein9Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for Q792Q4 (Rattus norvegicus)
Explore Q792Q4 
Go to UniProtKB:  Q792Q4
Entity Groups  
UniProt GroupQ792Q4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.169 
  • Space Group: P 41 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.771α = 90
b = 89.771β = 90
c = 89.771γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
Cootmodel building

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Robert A. Welch FoundationUnited StatesI-1366

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-16
    Type: Initial release
  • Version 1.1: 2017-09-27
    Changes: Author supporting evidence, Derived calculations
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Refinement description