title: Structure-activity relationship of the peptide binding-motif mediating the BRCA2:RAD51 protein-protein interaction.
abstract: RAD51 is a recombinase involved in the homologous recombination of double-strand breaks in DNA. RAD51 forms oligomers by binding to another molecule of RAD51 via an 'FxxA' motif, and the same recognition sequence is similarly utilised to bind BRCA2. We have tabulated the effects of mutation of this sequence, across a variety of experimental methods and from relevant mutations observed in the clinic. We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X-ray crystallography. Where possible, comparison between our tetrapeptide mutational study and the previously reported mutations is made, discrepancies are discussed and the importance of secondary structure in interpreting alanine scanning and mutational data of this nature is considered.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Duncan E
authors.initials: DE
authors.lastname: Scott
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: May
authors.initials: M
authors.lastname: Marsh
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Abell
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Marko
authors.initials: M
authors.lastname: Hyvönen
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D024682:BRCA2 Protein / Q000378:metabolism*; D017124:Conserved Sequence; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051135:Rad51 Recombinase / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D010455:Peptides; D051135:Rad51 Recombinase
keywords: RAD51; X-ray crystallography; alanine scanning; biophysics/ITC; peptides; protein-protein interaction