title: Mutant conformation of p53. Precise epitope mapping using a filamentous phage epitope library.
abstract: Many naturally occurring point mutations in the p53 gene lead to a proportion of the encoded protein molecules adopting a distinct, "mutant" conformation characterized by exposure of a normally cryptic epitope recognized by the monoclonal antibody PAb240. Here the PAb240 epitope is defined using a filamentous phage epitope library. The hexapeptides displayed by the PAb240-binding phage isolated from the library were all highly related and allowed both direct localization of the epitope and prediction of a specific interaction between PAb240 and Xenopus TFIIIA. This study demonstrates for the first time the power of phage epitope libraries in the precise definition of previously unmapped epitopes. Identification of the PAb240 epitope precisely defines a region of the p53 molecule structurally altered by the mutation-induced conformational shift.
authors.affiliation: Cell Transformation Research Group, University of Dundee, Scotland.
authors.forename: C W
authors.initials: CW
authors.lastname: Stephen
authors.forename: D P
authors.initials: DP
authors.lastname: Lane
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D001666:Binding Sites, Antibody; D002645:Chickens; D003001:Cloning, Molecular; D003090:Coliphages; D003429:Cross Reactions; D000939:Epitopes; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D035582:Transcription Factor TFIIIA; D014157:Transcription Factors / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology / Q000648:ultrastructure*; D014982:Xenopus laevis
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D035582:Transcription Factor TFIIIA; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53