PDBsum entry 2oqs

Peptide binding protein

PDB id: 2oqs

Contents

Protein chain

92 a.a. *

Ligands

ARG-ARG-GLU-THR-GLN-VAL

* Residue conservation analysis

PDB id:

2oqs

Name:

Peptide binding protein

Title:

Structure of the hdlg/sap97 pdz2 in complex with hpv-18 papillomavirus e6 peptide

Structure:

Disks large homolog 1. Chain: a. Fragment: second pdz domain, residues 318-406. Synonym: synapse-associated protein 97, sap-97, hdlg. Engineered: yes. C-terminal hpv-18 e6 peptide. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dlg1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in homo sapiens (human)

NMR struc:

30 models

Authors:

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

Key ref:

Y.Liu et al. (2007). Solution structure of the hDlg/SAP97 PDZ2 domain and its mechanism of interaction with HPV-18 papillomavirus E6 protein. Biochemistry, 46, 10864-10874. PubMed id: 17713926

Date:

01-Feb-07 Release date: 04-Sep-07

Protein chain

Q12959  (DLG1_HUMAN) -  Disks large homolog 1 from Homo sapiens

Seq: 904 a.a.

Struc: 92 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

Biochemistry 46:10864-10874 (2007)

PubMed id: 17713926

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

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

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.