2oqs

From Proteopedia

Revision as of 10:41, 23 January 2008

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 Aug 22;. PMID:17713926

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