Scanning the structure and antigenicity of HPV-16 E6 and E7 oncoproteins using antipeptide antibodies.
The structure and antigenicity of the HPV-16 E6 and E7 oncoproteins was studied using a set of antisera against overlapping synthetic peptides. We report that antigenic, mobile regions of the native proteins, as defined by reactivity with antipeptide antisera, occur at the N-termini of both E6 and E7 proteins, corresponding to regions of known or suspected protein-protein interactions. The putative zinc finger domains were consistently non-reactive, despite computer predictions of relatively high antigenicity, suggesting that the proposed zinc finger regions are held in stable secondary structures that the peptides were not able to mimic. In E6, the linker region between the two zinc fingers was antigenic, indicating that the two zinc finger structures might be able to articulate relative to one another by a flexible linker region. The highly antigenic N-terminal region of HPV-16 E7 was also found to be antigenic in E7 of both HPV-11 and HPV-18, indicating that the E7 proteins of different HPV types have similar antigenic structures. The identification of antigenic regions of the E6 and E7 proteins should be therefore be useful in the design of site-directed antibodies against E6 and E7 for numerous HPV types.
Stacey
S N
SN
Cancer Research Campaign Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Eklund
C
C
Jordan
D
D
Smith
N K
NK
Stern
P L
PL
Dillner
J
J
Arrand
J R
JR
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology*; D000918:Antibody Specificity; D001483:Base Sequence; D015153:Blotting, Western; D004273:DNA, Neoplasm / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000032:analysis* / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D010449:Peptide Mapping; D012097:Repressor Proteins; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology; D016335:Zinc Fingers
D000914:Antibodies, Viral; D004273:DNA, Neoplasm; C068651:E6 protein, Human papillomavirus type 16; D000939:Epitopes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16