Folding of Tetrameric p53: Oligomerization and Tumorigenic Mutations Induce Misfolding and Loss of Function

Journal of Molecular Biology

Volumn 395, Issue 4, 2010, Pages 705-716

  Lubin, David J ^a   Butler, James S ^b   Loh, Stewart N ^a  

^a State University of New York Upstate Medical University: College of Medicine   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

aggregation; cancer; DBD; protein stability; tetramerization

Indexed keywords

MONOMER; PROTEIN P53; TETRAMER; UREA;

ARTICLE; CARCINOGENESIS; CONTROLLED STUDY; LOSS OF FUNCTION MUTATION; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CONFORMATION; PROTEIN DENATURATION; PROTEIN DNA BINDING; PROTEIN FOLDING; PROTEIN STABILITY; THERMODYNAMICS;

EID: 73649087901     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2009.11.013     Document Type: Article

References (47)

1. Lane D.P. Cancer. p53, guardian of the genome. Nature 358 (1992) 15-16
2. Ko L.J., and Prives C. p53: puzzle and paradigm. Genes Dev. 10 (1996) 1054-1072
3. Hainaut P., Soussi T., Shomer B., Hollstein M., Greenblatt M., Hovig E., et al. Database of p53 gene somatic mutations in human tumors and cell lines: updated compilation and future prospects. Nucleic Acids Res. 25 (1997) 151-157
4. Cho Y., Gorina S., Jeffrey P.D., and Pavletich N.P. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265 (1994) 346-355
5. Butler J.S., and Loh S.N. Structure, function, and aggregation of the zinc-free form of the p53 DNA binding domain. Biochemistry 42 (2003) 2396-2403
6. Bullock A.N., Henckel J., DeDecker B.S., Johnson C.M., Nikolova P.V., Proctor M.R., et al. Thermodynamic stability of wild-type and mutant p53 core domain. Proc. Natl Acad. Sci. USA 94 (1997) 14338-14342
7. Wong K.-B., DeDecker B.S., Freund S.M., Proctor M.R., Bycroft M., and Fersht A.R. Hot-spot mutants of p53 core domain evince characteristic local structural changes. Proc. Natl Acad. Sci. USA 96 (1999) 8438-8442
8. Bullock A.N., Henckel J., and Fersht A.R. Quantitative analysis of residual folding and DNA binding in mutant p53 core domain: definition of mutant states for rescue in cancer therapy. Oncogene 19 (2000) 1245-1256
9. Butler J.S., and Loh S.N. Kinetic partitioning during folding of the p53 DNA binding domain. J. Mol. Biol. 350 (2005) 906-918
10. Butler J.S., and Loh S.N. Folding and misfolding mechanisms of the p53 DNA binding domain at physiological temperature. Protein Sci. 15 (2006) 2457-2465
11. Lee W., Harvey T.S., Yin Y., Yau P., Litchfield D., and Arrowsmith C.H. Solution structure of the tetrameric minimum transforming domain of p53. Nat. Struct. Biol. 1 (1994) 877-890
12. Clore G.M., Omichinsky J.G., Sakaguchi K., Zambrano N., Sakamoto H., Apella E., and Gronenborn A.M. High-resolution structure of the oligomerization domain of p53 by multidimensional NMR. Science (1994) 386-391
13. Jeffrey P.D., Gorina S., and Pavletich N.P. Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms. Science 267 (1995) 1498-1502
14. Mateu M.G., and Fersht A.R. Nine hydrophobic side chains are key determinants of the thermodynamic stability and oligomerization status of tumour suppressor p53 tetramerization domain. EMBO J. 17 (1998) 2748-2758
15. Mateau M.G., Sanchez Del Pino M.M., and Fersht A.R. Mechanism of folding and assembly of a small tetrameric protein domain from tumor suppressor p53. Nat. Struct. Biol. 6 (1999) 191-198
16. Natan E., Hirschberg D., Morgner N., Robinson C.V., and Fersht A.R. Ultraslow oligomerization equilibria of p53 and its implications. Proc. Natl Acad. Sci. USA 106 (2009) 14327-14332
17. Sakaguchi K. Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry 36 (1997) 10117-10124
18. Abraham J., Kelly J., Thibault P., and Benchimol S. Post-translational modification of p53 protein in response to ionizing radiation analyzed by mass spectrometry. J. Mol. Biol. 295 (1999) 853-864
19. Quinones A., and Rainov N.G. Identification of genotoxic stress in human cells by fluorescent monitoring of p53 expression. Mutat. Res. 494 (2001) 73-85
20. Rosario Fernandez-Fernandez M., Veprintsev D.B., and Fersht A.R. Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor. Proc. Natl Acad. Sci. USA 102 (2005) 4735-4740
21. Delphin C., Ronjat M., Deloulme J.C., Garin G., Debussche L., Higashimoto Y., et al. Calcium-dependent interaction of S100B with the C-terminal domain of the tumor suppressor p53. J. Biol. Chem. 274 (1999) 10539-10544
22. Wilder P.T., Lin J., Bair C.L., Charpentier T.H., Yang D., Liriano M., et al. Recognition of the tumor suppressor protein p53 and other protein targets by the calcium-binding protein S100B. Biochim. Biophys. Acta 1763 (2006) 1284-1297
23. Pietenpol J.A., Tokino T., Thiagalingam S., El-Deiry W.S., Kinzler K.W., and Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc. Natl Acad. Sci. USA 91 (1994) 1998-2002
24. Kawaguchi T., Kato S., Otsuka K., Watanabe G., Kumabe T., Tominaga T., et al. The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library. Oncogene 24 (2005) 6976-6981
25. Wang Y., Schwedes J.F., Parks D., Mann K., and Tegtmeyer P. Interaction of p53 with its consensus DNA binding site. Mol. Cell. Biol. 15 (1995) 2157-2165
26. Ho W.C., Fitzgerald M.X., and Marmorstein R. Structure of the p53 core domain dimer bound to DNA. J. Biol. Chem. 281 (2006) 20494-20502
27. Veprintsev D.B., Freund S.M.V., Andreeva A., Rutledge S.E., Tidow H., Cañadillas J.M.P., et al. Core domain interactions in full-length p53 in solution. Proc. Natl Acad. Sci. USA 103 (2006) 21115-21119
28. Tidow H., Melero R., Mylonas E., Freund S.M.V., Grossman J.G., Carazo J.M., et al. Quaternary structures of tumor suppressor p53 and a specific p53-DNA complex. Proc. Natl Acad. Sci. USA 104 (2007) 12324-12329
29. Bell S., Klein C., Müller L., Hansen S., and Buchner J. p53 contains large unstructured regions in its native state. J. Mol. Biol. 322 (2002) 917-927
30. Ang H.C., Joerger A.C., Mayer S., and Fersht A.R. Effects of common cancer mutations on stability and DNA binding of full-length p53 compared with isolated core domains. J. Biol. Chem. 281 (2006) 21934-21941
31. Weinberg R.L., Freund S.M., Veprintsev D.B., Bycroft M., and Fersht A.R. Regulation of DNA binding of p53 by its C-terminal domain. J. Mol. Biol. 342 (2004) 801-811
32. Davison T.S., Yin P., Nie E., Kay C., and Arrowsmith C.H. Characterization of the oligomerization defects of two p53 mutants found in families with Li-Fraumeni and Li-Fraumeni-like syndrome. Oncogene 17 (1998) 651-656
33. Friedler A., Veprintsev D.B., Hansson L.O., and Fersht A.R. Kinetic instability of p53 core domain mutants. J. Biol. Chem. 278 (2003) 24108-24112
34. 2+-dependent misfolding of the p53 DNA binding domain. Biochemistry 46 (2007) 2630-2639
35. Kastan M.B., Zhan Q., el-Deiry W.S., Carrier F., Jacks T., Walsh W.V., et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71 (1992) 587-597
36. Tu C., Tan Y.H., Shaw G., Zhou Z., Bai Y., Luo R., and Ji X. Impact of low-frequency hotspot mutation R282Q on the structure of p53 DNA-binding domain as revealed by crystallography at 1.54 angstroms resolution. Acta Crystallogr. Sect. D 64 (2008) 471-477
37. Poon G.M.K., Brokx R.D., Sung M., and Gariepy J. Tandem dimerization of the human p53 tetramerization domain stabilizes a primary dimer intermediate and dramatically enhances its oligomeric stability. J. Mol. Biol. 365 (2007) 1217-1231
38. Friedler A., DeDecker B.S., Freund S.M.V., Blair C., Rüdiger S., and Fersht A.R. Structural distortion of p53 by the mutation R249S and its rescue by a designed peptide: implications for "mutant conformation". J. Mol. Biol. 336 (2004) 187-196
39. Robinson C.R., and Sauer R.T. Equilibrium stability and sub-millisecond refolding of a designed single-chain Arc repressor. Biochemistry 35 (1996) 13878-13884
40. Robinson C.R., and Sauer R.T. Optimizing the stability of single-chain proteins by linker length and composition mutagenesis. Proc. Natl Acad. Sci. USA 95 (1998) 5929-5934
41. Nikolova P.V., Henckel J., Lane D.P., and Fersht A.R. Semirational design of active tumor suppressor p53 DNA binding domain with enhanced stability. Proc. Natl Acad. Sci. USA 95 (1998) 14675-14680
42. Joerger A.C., Allen M.D., and Fersht A.R. Crystal structure of a superstable mutant of human p53 core domain. Insights into the mechanism of rescuing oncogenic mutations. J. Biol. Chem. 279 (2004) 1291-1296
43. Kantarci N., Doruker P., and Haliloglu T. Cooperative fluctuations point to the dimerization interface of p53 core domain. Biophys. J. 91 (2006) 421-432
44. Rippin T.M., Freund S.M.V., Veprintsev D.B., and Fersht A.R. Recognition of DNA by p53 core domain and location of intermolecular contacts of cooperative binding. J. Mol. Biol. 319 (2002) 351-358
45. Ma B., Pan Y., Gunasekaran K., Venkataraghaven R.B., Levine A.J., and Nussinov R. Comparison of protein-protein interfaces in the p53-DNA crystal structures: towards elucidation of the biological interface. Proc. Natl Acad. Sci. USA 102 (2005) 3988-3993
46. Liang S.H., and Clarke M.F. Regulation of p53 localization. Eur. J. Biochem. 268 (2001) 2779-2783
47. Hupp T.R., Meek D.W., Midgley C.A., and Lane D.P. Regulation of the specific DNA binding function of p53. Cell 71 (1992) 875-886