2OQS

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

Summary for 2OQS

• Entry DOI: 10.2210/pdb2oqs/pdb
• Descriptor: Disks large homolog 1, C-terminal HPV-18 E6 peptide (2 entities in total)
• Functional Keywords: hpv e6, hdlg pdz domain, protein-peptide complex, peptide-binding protein, peptide binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Peripheral membrane protein (By similarity): Q12959
• Total number of polymer chains: 2
• Total formula weight: 11190.77

Authors

Liu, Y.,Baleja, J.D.,Henry, G.D.,Hegde, R.S. (deposition date: 2007-02-01, release date: 2007-09-04, Last modification date: 2023-12-27)

Primary citation

Liu, Y.,Henry, G.D.,Hegde, R.S.,Baleja, J.D.
Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein.
Biochemistry, 46:10864-10874, 2007

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.

PubMed: 17713926
DOI: 10.1021/bi700879k

Experimental method

SOLUTION NMR