Characterisation of epitopes on human p53 using phage-displayed peptide libraries: insights into antibody-peptide interactions

Journal of Molecular Biology
C W StephenD P Lane

Abstract

We previously described the use of a phage-displayed library of random hexapeptides to define and localise the epitope on the human tumor suppressor protein p53 recognised by the monoclonal antibody PAb240. Here we have extended these results to a further eight anti-p53 monoclonal antibodies and to two further libraries, which display 12-mer and 20-mer peptides, respectively. First, we showed that selection of PAb240 binding clones from the 12-mer and 20-mer libraries gives essentially identical results to those obtained by screening the 6-mer library. Second, we used the 6-mer and 12-mer libraries to define the detailed specificity profiles of six antibodies (DO-1, DO-2, DO-7, Bp53-11, Bp53-12 and Bp53-19), which recognise the same short, highly immunogenic N-terminal segment of p53. Finally, we employed all three libraries to reveal the distinct mechanisms by which PAb421 and PAb122, two monoclonal antibodies that allosterically activate sequence-specific DNA binding by p53, react specifically with the same positively-charged C-terminal segment. In each case the epitope locations inferred from the selected sequences were confirmed by probing an array of overlapping synthetic peptides representing the primary sequence of p53. ...Continue Reading

Citations

Jun 6, 2009·Investigational New Drugs·Eva RoubalováBorivoj Vojtesek
Nov 4, 2000·The Biochemical Journal·T R HuppK L Ball
Nov 11, 2010·Molecular & Cellular Proteomics : MCP·Rebecca F HalperinStephen Albert Johnston
Sep 1, 2005·Genes & Development·Jean-Christophe BourdonDavid P Lane
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·D P Lane
Aug 21, 2002·Journal of Virology·Dilip DeyThomas L Benjamin
Jan 20, 2004·Molecular and Cellular Biology·Koji NakadeBohdan Wasylyk
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Richard OdegripDuncan McGregor
Jul 24, 2002·The Journal of Cell Biology·J-C BourdonD P Lane
Dec 14, 2011·Cancer Biology & Therapy·Lorna Jane WarnockJo Milner
Jun 27, 1997·Journal of Molecular Biology·A BöttgerD P Lane
Jul 10, 2004·Cell·Dimitris P XirodimasDavid P Lane
Dec 27, 2005·Experimental Eye Research·Yevgeny TendlerOren Zinder
Oct 20, 2005·Journal of Bioscience and Bioengineering·Fumiaki UchiyamaNoritaka Tokui
Apr 10, 2007·Oral Oncology·Majid EbrahimiKarin Nylander
May 18, 1999·International Journal of Cancer. Journal International Du Cancer·P HammelY Remvikos
Sep 23, 2003·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·R NenutilB Vojtesek
Dec 17, 2003·British Journal of Cancer·K J RolfeC W Perrett
Jul 3, 2013·ORL; Journal for Oto-rhino-laryngology and Its Related Specialties·José de Assis Silva JúniorSimone Queiroz Chaves Lourenço
Sep 5, 2002·FEBS Letters·Henrie A A J KorthoutMei Wang
Dec 1, 2004·Journal of Peptide Science : an Official Publication of the European Peptide Society·Stephane CoulonDaniel Baty
Feb 15, 2003·FEBS Letters·Suzanne CamusSonia Lain
Jan 25, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Peter MolekTomaz Bratkovic

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