Analysis of specificity determinants in the interactions of different HPV E6 proteins with their PDZ domain-containing substrates.
The E6 oncoproteins of the cancer-associated human papillomaviruses (high-risk HPV types) characteristically have a PDZ-binding motif at their extreme carboxy-termini. However, they interact with only some of the PDZ domain-containing proteins in the human proteome and, despite many of these proteins having multiple PDZ domains, they interact specifically through only one of those domains. Previous work has shown that the exact sequence of the C-terminal PDZ-binding motif of E6 affects substrate selection, and recently we have shown that an E6 residue peripheral to the binding motif also contributes to the specificity of binding. Here we show that substrate specificity of the HPV E6 PDZ binding is modulated both by the amino acid residues upstream of the binding domain and by the non-canonical residues within it. Using this data we have begun to construct a scheme of substrate preferences for E6 proteins from different HPV types.
Thomas
Miranda
M
Tumour Virology Laboratory, I.C.G.E.B., Padriciano 99, 34012 Trieste, Italy. miranda@icgeb.org
Dasgupta
Jhimli
J
Zhang
Yi
Y
Chen
Xiaojiang
X
Banks
Lawrence
L
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054731:PDZ Domains / Q000502:physiology*; D030361:Papillomavirus Infections / Q000628:therapy; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D051528:Guanylate Kinases; C113338:MAGI1 protein, human