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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.

SUBMITTER: Scott DE

PROVIDER: S-EPMC4855620 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Structure-activity relationship of the peptide binding-motif mediating the BRCA2:RAD51 protein-protein interaction.

Scott Duncan E DE Marsh May M Blundell Tom L TL Abell Chris C Hyvönen Marko M

FEBS letters 20160406 8

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 ...[more]

PMID: 26992456

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