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

FEBS Letters

Volumn 590, Issue 8, 2016, Pages 1094-1102

  Scott, Duncan E ^a   Marsh, May ^a,b   Blundell, Tom L ^a   Abell, Chris ^a   Hyvönen, Marko ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b PAUL SCHERRER INSTITUTE   (Switzerland)

Author keywords

alanine scanning; biophysics ITC; peptides; protein protein interaction; RAD51; X ray crystallography

Indexed keywords

ALANINE; BRCA2 PROTEIN; GLYCINE; PHENYLALANINE; RAD51 PROTEIN; TETRAPEPTIDE; THREONINE; TRYPTOPHAN; BRCA2 PROTEIN, HUMAN; PEPTIDE; PROTEIN BINDING;

AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; ISOTHERMAL TITRATION CALORIMETRY; MUTATION; PEPTIDE BINDING MOTIF; PRIORITY JOURNAL; PROTEIN MOTIF; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY; AMINO ACID SEQUENCE; CONSERVED SEQUENCE; GENETICS; HUMAN; METABOLISM; MOLECULAR MODEL;

AMINO ACID MOTIFS; AMINO ACID SEQUENCE; BRCA2 PROTEIN; CONSERVED SEQUENCE; HUMANS; MODELS, MOLECULAR; MUTATION; PEPTIDES; PROTEIN BINDING; PROTEIN STRUCTURE, SECONDARY; RAD51 RECOMBINASE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84963641779     PISSN: 00145793     EISSN: 18733468     Source Type: Journal    
DOI: 10.1002/1873-3468.12139     Document Type: Article

References (29)

1. Shinohara A, Ogawa H, and, Ogawa T, (1992) RAD51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69, 457-470.
2. Venkitaraman AR, (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108, 171-182.
3. Davies AA, Masson J-Y, McIlwraith MJ, Stasiak AZ, Stasiak A, Venkitaraman AR, and, West SC, (2001) Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol Cell 7, 273-282.
4. Stratton MR, and, Rahman N, (2008) The emerging landscape of breast cancer susceptibility. Nat Genet 40, 17-22.
5. Begg CB, Haile RW, Borg A, Malone KE, Concannon P, Thomas DC, Langholz B, Bernstein L, Olsen JH, Lynch CF, et al,. (2008) Variation of breast cancer risk among BRCA1/2 carriers. JAMA 299, 194-201.
6. Bernier J, and, Poortmans P, (2015) Clinical relevance of normal and tumour cell radiosensitivity in BRCA1/BRCA2 mutation carriers: a review. Breast 24, 100-106.
7. Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C, Sands A, Eichele G, Hasty P, and, Bradley A, (1997) Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 386, 804-810.
8. Scott DE, Coyne AG, Venkitaraman A, Blundell TL, Abell C, and, Hyvonen M, (2015) Small-molecule inhibitors that target protein-protein interactions in the RAD51 family of recombinases. ChemMedChem 10, 296-303.
9. Lo T, Pellegrini L, Venkitaraman AR, and, Blundell TL, (2003) Sequence fingerprints in BRCA2 and RAD51: implications for DNA repair and cancer. DNA Repair 2, 1015-1028.
10. Keskin O, Ma B, and, Nussinov R, (2005) Hot regions in protein-protein interactions: the organization and contribution of structurally conserved hot spot residues. J Mol Biol 345, 1281-1294.
11. Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, and, Venkitaraman AR, (2002) Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature 420, 287-293.
12. Rajendra E, and, Venkitaraman AR, (2010) Two modules in the BRC repeats of BRCA2 mediate structural and functional interactions with the RAD51 recombinase. Nucleic Acids Res 38, 82-96.
13. Nomme J, Renodon-Cornière A, Asanomi Y, Sakaguchi K, Stasiak AZ, Stasiak A, Norden B, Tran V, and, Takahashi M, et al,. (2010) Design of potent inhibitors of human RAD51 recombinase based on BRC motifs of BRCA2 protein: modeling and experimental validation of a chimera peptide. J Med Chem 53, 5782-5791.
14. Caputo S, Benboudjema L, Sinilnikova O, Rouleau E, Beroud C, Lidereau R, and the French BRCA GGC Consortium (2012) Description and analysis of genetic variants in French hereditary breast and ovarian cancer families recorded in the UMD-BRCA1/BRCA2 databases. Nucleic Acids Res 40, D992-D1002.
15. Scott DE, Ehebauer MT, Pukala T, Marsh M, Blundell TL, Venkitaraman AR, Abell C, and, Hyvonen M, (2013) Using a fragment-based approach to target protein-protein interactions. ChemBioChem 14, 332-342.
16. Turnbull WB, and, Daranas AH, (2003) On the value of c: can low affinity systems be studied by isothermal titration calorimetry? J Am Chem Soc 125, 14859-14866.
17. Murshudov GN, Skubák P, Lebedev AA, Pannu NS, Steiner RA, Nicholls RA, Winn MD, Long F, and, Vagin AA, (2011) REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr 67, 355-367.
18. Murshudov GN, Vagin AA, and, Dodson EJ, (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr 53, 240-255.
19. Adams PD, Afonine PV, Bunkóczi G, Chen VB, Davis IW, Echols N, Headd JJ, Hung LW, Kapral GJ, Grosse-Kunstleve RW, et al,. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66, 213-221.
20. Emsley P, and, Cowtan K, (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60, 2126-2132.
21. Crooks GE, Hon G, Chandonia JM, and, Brenner SE, (2004) WebLogo: a sequence logo generator. Genome Res 14, 1188-1190.
22. Carreira A, and, Kowalczykowski SC, (2011) Two classes of BRC repeats in BRCA2 promote RAD51 nucleoprotein filament function by distinct mechanisms. Proc Natl Acad Sci USA 108, 10448-10453.
23. Wu Y, He Y, Moya IA, Qian X, and, Luo Y, (2004) Crystal structure of archaeal recombinase RADA: a snapshot of its extended conformation. Mol Cell 15, 423-435.
24. Klebe G, (2015) Applying thermodynamic profiling in lead finding and optimization. Nat Rev Drug Discov 14, 95-110.
25. Chodera JD, and, Mobley DL, (2013) Entropy-enthalpy compensation: role and ramifications in biomolecular ligand recognition and design. Annu Rev Biophys 42, 121-142.
26. Lichtarge O, and, Sowa ME, (2002) Evolutionary predictions of binding surfaces and interactions. Curr Opin Struct Biol 12, 21-27.
27. Conway AB, Lynch TW, Zhang Y, Fortin GS, Fung CW, Symington LS, and, Rice PA, (2004) Crystal structure of a Rad51 filament. Nat Struct Mol Biol 11, 791-796.
28. Qian X, Wu Y, He Y, and, Luo Y, (2005) Crystal structure of Methanococcus voltae RadA in complex with ADP: hydrolysis-induced conformational change. Biochemistry 44, 13753-13761.
29. Shin DS, Pellegrini L, Daniels DS, Yelent B, Craig L, Bates D, Yu DS, Shivji MK, Hitomi C, Arvai AS, et al,. (2003) Full-length archaeal RAD51 structure and mutants: mechanisms for RAD51 assembly and control by BRCA2. EMBO J 22, 4566-4576.