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2oqs
From Proteopedia
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| Gene: | DLG1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of the hDLG/SAP97 PDZ2 in complex with HPV-18 papillomavirus E6 peptide
Overview
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.
About this Structure
2OQS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein., Liu Y, Henry GD, Hegde RS, Baleja JD, Biochemistry. 2007 Sep 25;46(38):10864-74. Epub 2007 Aug 22. PMID:17713926
Page seeded by OCA on Thu Mar 20 18:03:19 2008
