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

Yuqi Liu, Zhiguo Liu, Elliot Androphy, Jason Chen, James D. Baleja

Research output: Contribution to journalArticle

48 Citations (Scopus)

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 α-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 Å. 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.

Original languageEnglish (US)
Pages (from-to)7421-7431
Number of pages11
JournalBiochemistry
Volume43
Issue number23
DOIs
StatePublished - Jun 15 2004
Externally publishedYes

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Peptides
Scaffolds
Proteins
Circular dichroism spectroscopy
Zinc Fingers
Consensus Sequence
Viral Proteins
Circular Dichroism
Bioactivity
Leucine
Conformations
Zinc
Spectrum Analysis
Carrier Proteins
Nuclear magnetic resonance
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Design and characterization of helical peptides that inhibit the E6 protein of papillomavirus. / Liu, Yuqi; Liu, Zhiguo; Androphy, Elliot; Chen, Jason; Baleja, James D.

In: Biochemistry, Vol. 43, No. 23, 15.06.2004, p. 7421-7431.

Research output: Contribution to journalArticle

Liu, Yuqi ; Liu, Zhiguo ; Androphy, Elliot ; Chen, Jason ; Baleja, James D. / Design and characterization of helical peptides that inhibit the E6 protein of papillomavirus. In: Biochemistry. 2004 ; Vol. 43, No. 23. pp. 7421-7431.
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