2OQS

Structure of the hDLG/SAP97 PDZ2 in complex with HPV-18 papillomavirus E6 peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 30 
  • Selection Criteria: all calculated structures submitted 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein.

Liu, Y.Henry, G.D.Hegde, R.S.Baleja, J.D.

(2007) Biochemistry 46: 10864-10874

  • DOI: https://doi.org/10.1021/bi700879k
  • Primary Citation of Related Structures:  
    2OQS

  • PubMed Abstract: 

    The E6 protein from high-risk types of human papillomavirus (HPV) binds PDZ-domain containing proteins and targets them for degradation. We used isothermal titration calorimetry to measure the interaction of a peptide from the C-terminus of HPV-18 E6 to the second PDZ domain (PDZ2) from the human homologue of the Drosophila discs large tumor suppressor protein (hDlg). Isothermal titration calorimetry experiments with a series of peptides showed that HPV-18 E6 bound hDlg PDZ2 about 5-fold stronger than HPV-16 E6, that the contribution of Arg154 to binding was about 1 kcal/mol, and that the binding was disabled by phosphorylation at Thr156. We then used NMR to determine the solution structure of the complex of PDZ2 bound to the HPV-18 E6 peptide. The resultant structures were of high quality and had backbone root-mean-square deviations of less than 0.5 A. The structure shows a novel mode of interaction in which six residues of the HPV-18 E6 peptide are contacted by the PDZ2 domain, in contrast to the typical four residues used by class I PDZ domains. Molecular dynamics simulations supported a model in which the C- and N-terminal ends of the peptide had different mobilities within the complex. Comparison of the NMR complex structure to previously determined X-ray structures of PDZ2 by itself and bound to different peptides allows a description of conformational changes required for PDZ2 to bind to HPV-18 E6.


  • Organizational Affiliation

    Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Disks large homolog 197Homo sapiensMutation(s): 0 
Gene Names: DLG1
UniProt & NIH Common Fund Data Resources
Find proteins for Q12959 (Homo sapiens)
Explore Q12959 
Go to UniProtKB:  Q12959
PHAROS:  Q12959
GTEx:  ENSG00000075711 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ12959
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
C-terminal HPV-18 E6 peptide6N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 30 
  • Selection Criteria: all calculated structures submitted 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-09-04
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2022-03-16
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.3: 2023-12-27
    Changes: Data collection