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

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

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

Yuqi Liu,Gillian D Henry,Rashmi S Hegde,James D Baleja,

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.

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

Y Liu,GD Henry,RS Hegde,JD Baleja,

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

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Biochemistry

VOLUME: 46

Page Numbers: 10864-74

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 22

MONTH: 08

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 370623

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

KEYWORDS: Solutions

MESH TERMS: metabolism

Chemical & Substance for Abstract: Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein. Information

Substance Name: Solutions

Registry Number: 0

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

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

Country: United States

AGENCY: United States NIAID

GRANT: AI38001

ACRONYM: AI

MEDLINETA: Biochemistry

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