Summary auto-generated
This study identified a conserved binding motif used by human papillomavirus type 16 (HPV-16) E6 protein to interact with multiple cellular proteins. Using yeast two-hybrid screening of a peptide library, researchers isolated five E6-binding peptides, four containing an E/D-L/I/F-L/V-G consensus motif and one derived from tuberin containing a D-I-L-G variant. Comparison with known E6 binding proteins E6AP and E6BP revealed homology to this same motif region. Synthetic peptides containing the ELLG motif successfully blocked E6 binding to both E6AP and E6BP in pulldown assays. The authors characterized the E6 binding domain as requiring the E/D-L/I/F-L/V-G core motif plus upstream hydrophobic residues, at least one acidic residue, and notably, the complete absence of basic residues. These findings explain how HPV-16 E6 interacts with diverse cellular proteins through a structurally similar binding interface, providing molecular insight into the viral oncoproteins's transforming mechanisms beyond p53 degradation.
Key findings
- A conserved E/D-L/I/F-L/V-G binding motif was identified in HPV-16 E6 interacting proteins including E6AP, E6BP, and tuberin
- Synthetic peptides containing the ELLG motif competitively inhibited E6 binding to both E6AP and E6BP, confirming motif functionality
- The complete E6 binding domain requires hydrophobic residues upstream of the core motif, at least one acidic residue, and absence of basic residues
- The identified motif is present in the previously characterized 18-amino acid E6AP binding domain, validating the findings in an independent system
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Abstract
A 16-mer peptide library was screened using the yeast two-hybrid system to identify peptides which specifically interact with the human papillomavirus type 16 (HPV-16) E6 protein. Four different peptides were identified, three of which contained an E-L-L/V-G motif. A fifth E6 binding peptide, derived from the putative tumour suppressor protein tuberin, was identified during a two-hybrid screen of a HeLa cDNA expression library. This peptide contained a D-I-L-G motif. Homology to the peptides was found within the E6 binding proteins E6-AP and E6-BP. A synthetic peptide containing the ELLG motif blocked the interaction of E6 with both E6-AP and E6-BP. The data suggest that E6 interacts through a structurally similar binding domain present within a number of cellular proteins.