PDBsum entry 1rim

De novo protein

PDB id: 1rim

Contents

Protein chain

33 a.a. *

* Residue conservation analysis

PDB id:

1rim

Name:

De novo protein

Title:

E6-binding zinc finger (e6apc2)

Structure:

E6apc2 peptide. Chain: a. Engineered: yes

Source:

Synthetic: yes. Other_details: the peptide was chemically synthesized

NMR struc:

29 models

Authors:

Y.Liu,Z.Liu,E.Androphy,J.Chen,J.D.Baleja

Key ref:

Y.Liu et al. (2004). Design and characterization of helical peptides that inhibit the E6 protein of papillomavirus. Biochemistry, 43, 7421-7431. PubMed id: 15182185 DOI: 10.1021/bi049552a

Date:

17-Nov-03 Release date: 03-Aug-04

Protein chain

No UniProt id for this chain

Struc: 33 a.a.

DOI no: 10.1021/bi049552a

Biochemistry 43:7421-7431 (2004)

PubMed id: 15182185

Design and characterization of helical peptides that inhibit the E6 protein of papillomavirus.

Y.Liu, Z.Liu, E.Androphy, J.Chen, J.D.Baleja.

ABSTRACT

The E6 protein from HPV type 16 binds proteins containing a seven-residue leucine-containing motif. Previous work demonstrated that peptides containing the consensus sequence are a mixture of alpha-helix and unstructured conformations. To design monomeric E6-binding peptides that are stable in aqueous solution, we used a protein grafting approach where the critical residues of the E6-binding motif of E6-associated protein, E6AP, LQELLGE, were incorporated into exposed helices of two stably folded peptide scaffolds. One series was built using the third zinc finger of the Sp1 protein, which contains a C-terminal helix. A second series was built using a Trp-cage scaffold, which contains an N-terminal helix. The chimeric peptides had very different activities in out-competing the E6-E6AP interaction. We characterized the peptides by circular dichroism spectroscopy and determined high-resolution structures by NMR methods. The E6-binding consensus motif was found to be helical in the high-quality structures, which had backbone root-mean-square deviations of less than 0.4 A. We have successfully grafted the E6-binding motif into two parent peptides to create ligands that have biological activity while preserving the stable, native fold of their scaffolds. The data also indicate that conformational change is common in E6-binding proteins during the formation of the complex with the viral E6 protein.