Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 15 July 1994:
Vol. 265. no. 5170, pp. 386 - 391
DOI: 10.1126/science.8023159
Prev | Table of Contents | Next

Articles

Science, Vol 265, Issue 5170, 386-391
Copyright © 1994 by American Association for the Advancement of Science

articles

High-resolution structure of the oligomerization domain of p53 by multidimensional NMR

GM Clore, JG Omichinski, K Sakaguchi, N Zambrano, H Sakamoto, E Appella, and AM Gronenborn

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

The three-dimensional structure of the oligomerization domain (residues 319 to 360) of the tumor suppressor p53 has been solved by multidimensional heteronuclear magnetic resonance (NMR) spectroscopy. The domain forms a 20-kilodalton symmetric tetramer with a topology made up from a dimer of dimers. The two primary dimers each comprise two antiparallel helices linked by an antiparallel beta sheet. One beta strand and one helix are contributed from each monomer. The interface between the two dimers forming the tetramer is mediated solely by helix-helix contacts. The overall result is a symmetric, four-helix bundle with adjacent helices oriented antiparallel to each other and with the two antiparallel beta sheets located on opposing faces of the molecule. The tetramer is stabilized not only by hydrophobic interactions within the protein core but also by a number of electrostatic interactions. The implications of the structure of the tetramer for the biological function of p53 are discussed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Functional four-base A/T gap core sequence CATTAG of P53 response elements specifically bound tetrameric P53 differently than two-base A/T gap core sequence CATG bound both dimeric and tetrameric P53.
B.-H. Cai, J.-Y. Chen, M.-H. Lu, L.-T. Chang, H.-C. Lin, Y.-M. Chang, and C.-F. Chao (2009)
Nucleic Acids Res. 37, 1984-1990
   Abstract »    Full Text »    PDF »
p53 Oligomerization Is Essential for Its C-terminal Lysine Acetylation.
Y. Itahana, H. Ke, and Y. Zhang (2009)
J. Biol. Chem. 284, 5158-5164
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 ORF50/Rta Lytic Switch Protein Functions as a Tetramer.
W. Bu, K. D. Carroll, D. Palmeri, and D. M. Lukac (2007)
J. Virol. 81, 5788-5806
   Abstract »    Full Text »    PDF »
The Effects of Mutations at Position 253 on the Thermostability of the Bacillus subtilis 3-Isopropylmalate Dehydrogenase Subunit Interface.
T. Ohkuri and A. Yamagishi (2007)
J. Biochem. 141, 791-797
   Abstract »    Full Text »    PDF »
Structural Basis for p53 Binding-induced DNA Bending.
Y. Pan and R. Nussinov (2007)
J. Biol. Chem. 282, 691-699
   Abstract »    Full Text »    PDF »
Recognition of RNA by the p53 tumor suppressor protein in the yeast three-hybrid system..
K. J.-L. RILEY, L. A. CASSIDAY, A. KUMAR, and L. J. MAHER III (2006)
RNA 12, 620-630
   Abstract »    Full Text »    PDF »
Structural Details on mdm2-p53 Interaction.
S.-W. Chi, S.-H. Lee, D.-H. Kim, M.-J. Ahn, J.-S. Kim, J.-Y. Woo, T. Torizawa, M. Kainosho, and K.-H. Han (2005)
J. Biol. Chem. 280, 38795-38802
   Abstract »    Full Text »    PDF »
Structure of {lambda} CII: Implications for recognition of direct-repeat DNA by an unusual tetrameric organization.
A. B. Datta, S. Panjikar, M. S. Weiss, P. Chakrabarti, and P. Parrack (2005)
PNAS 102, 11242-11247
   Abstract »    Full Text »    PDF »
Comparison of the protein-protein interfaces in the p53-DNA crystal structures: Towards elucidation of the biological interface.
B. Ma, Y. Pan, K. Gunasekaran, R. B. Venkataraghavan, A. J. Levine, and R. Nussinov (2005)
PNAS 102, 3988-3993
   Abstract »    Full Text »    PDF »
Binding of Rad51 and Other Peptide Sequences to a Promiscuous, Highly Electrostatic Binding Site in p53.
A. Friedler, D. B. Veprintsev, T. Rutherford, K. I. von Glos, and A. R. Fersht (2005)
J. Biol. Chem. 280, 8051-8059
   Abstract »    Full Text »    PDF »
Analysis and prediction of leucine-rich nuclear export signals.
T. la Cour, L. Kiemer, A. Molgaard, R. Gupta, K. Skriver, and S. Brunak (2004)
Protein Eng. Des. Sel. 17, 527-536
   Abstract »    Full Text »    PDF »
Understanding the function-structure and function-mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis.
S. Kato, S.-Y. Han, W. Liu, K. Otsuka, H. Shibata, R. Kanamaru, and C. Ishioka (2003)
PNAS 100, 8424-8429
   Abstract »    Full Text »    PDF »
Biogenesis of p53 Involves Cotranslational Dimerization of Monomers and Posttranslational Dimerization of Dimers. IMPLICATIONS ON THE DOMINANT NEGATIVE EFFECT.
C. D. Nicholls, K. G. McLure, M. A. Shields, and P. W. K. Lee (2002)
J. Biol. Chem. 277, 12937-12945
   Abstract »    Full Text »    PDF »
Modeling multi-component protein-DNA complexes: the role of bending and dimerization in the complex of p53 dimers with DNA.
A. Lebrun, R. Lavery, and H. Weinstein (2001)
Protein Eng. Des. Sel. 14, 233-243
   Abstract »    Full Text »    PDF »
Heterogeneity in the Clinical Phenotype of TP53 Mutations in Breast Cancer Patients.
J. Alsner, M. Yilmaz, P. Guldberg, L. L. Hansen, and J. Overgaard (2000)
Clin. Cancer Res. 6, 3923-3931
   Abstract »    Full Text »
p53 Mutations and Expression in Breast Carcinoma in Situ.
J. Lukas, N. Niu, and M. F. Press (2000)
Am. J. Pathol. 156, 183-191
   Abstract »    Full Text »    PDF »
An ATP/ADP-Dependent Molecular Switch Regulates the Stability of p53-DNA Complexes.
A. L. Okorokov and J. Milner (1999)
Mol. Cell. Biol. 19, 7501-7510
   Abstract »    Full Text »    PDF »
Reactivation of Mutant p53 through Interaction of a C-Terminal Peptide with the Core Domain.
G. Selivanova, L. Ryabchenko, E. Jansson, V. Iotsova, and K. G. Wiman (1999)
Mol. Cell. Biol. 19, 3395-3402
   Abstract »    Full Text »    PDF »
Calcium-dependent Interaction of S100B with the C-terminal Domain of the Tumor Suppressor p53.
C. Delphin, M. Ronjat, J. C. Deloulme, G. Garin, L. Debussche, Y. Higashimoto, K. Sakaguchi, and J. Baudier (1999)
J. Biol. Chem. 274, 10539-10544
   Abstract »    Full Text »    PDF »
p53 Sites Acetylated In Vitro by PCAF and p300 Are Acetylated In Vivo in Response to DNA Damage.
L. Liu, D. M. Scolnick, R. C. Trievel, H. B. Zhang, R. Marmorstein, T. D. Halazonetis, and S. L. Berger (1999)
Mol. Cell. Biol. 19, 1202-1209
   Abstract »    Full Text »    PDF »
p73 Function Is Inhibited by Tumor-Derived p53 Mutants in Mammalian Cells.
C. J. Di Como, C. Gaiddon, and C. Prives (1999)
Mol. Cell. Biol. 19, 1438-1449
   Abstract »    Full Text »    PDF »
A Role for Groucho Tetramerization in Transcriptional Repression.
G. Chen, P. H. Nguyen, and A. J. Courey (1998)
Mol. Cell. Biol. 18, 7259-7268
   Abstract »    Full Text »
Cooperation of a Single Lysine Mutation and a C-terminal Domain in the Cytoplasmic Sequestration of the p53 Protein.
S.-H. Liang, D. Hong, and M. F. Clarke (1998)
J. Biol. Chem. 273, 19817-19821
   Abstract »    Full Text »    PDF »
Review : p53 in the pathogenesis, diagnosis, and treatment of cancer.
E. Perz and J. G. Kuhn (1998)
Journal of Oncology Pharmacy Practice 4, 75-102
   Abstract »    PDF »
Identification of an additional negative regulatory region for p53 sequence-specific DNA binding.
B. F. Muller-Tiemann, T. D. Halazonetis, and J. J. Elting (1998)
PNAS 95, 6079-6084
   Abstract »    Full Text »    PDF »
Deletion of the Saccharomyces cerevisiae TRR1 Gene Encoding Thioredoxin Reductase Inhibits p53-dependent Reporter Gene Expression.
G. D. Pearson and G. F. Merrill (1998)
J. Biol. Chem. 273, 5431-5434
   Abstract »    Full Text »    PDF »
HSP70 Binding Sites in the Tumor Suppressor Protein p53.
A. M. Fourie, T. R. Hupp, D. P. Lane, B.-C. Sang, M. S. Barbosa, J. F. Sambrook, and M.-J. H. Gething (1997)
J. Biol. Chem. 272, 19471-19479
   Abstract »    Full Text »    PDF »
alpha -Helical Protein Assembly Motifs.
W. D. Kohn, C. T. Mant, and R. S. Hodges (1997)
J. Biol. Chem. 272, 2583-2586
   Full Text »    PDF »
Mouse RAD50 Has Limited Epitopic Homology to p53 and Is Expressed in the Adult Myocardium.
K. K. Kim, A. I. Daud, S. C. Wong, L. Pajak, S.-C. Tsai, H. Wang, W. J. Henzel, and L. J. Field (1996)
J. Biol. Chem. 271, 29255-29264
   Abstract »    Full Text »    PDF »
Allosteric Regulation of the Thermostability and DNA Binding Activity of Human p53 by Specific Interacting Proteins.
S. Hansen, T. R. Hupp, and D. P. Lane (1996)
J. Biol. Chem. 271, 3917-3924
   Abstract »    Full Text »    PDF »
Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 angstroms.
P. Jeffrey, S Gorina, and N. Pavletich (1995)
Science 267, 1498-1502
   Abstract »    PDF »
Interhelical angles in the solution structure of the oligomerization domain of p53: correction.
G. Clore, J. Omichinski, K Sakaguchi, N Zambrano, H Sakamoto, E Appella, and A. Gronenborn (1995)
Science 267, 1515-1516
   PDF »
CMV-p53 interaction may help explain clogged arteries.
J Marx (1994)
Science 265, 320
   PDF »
p53: a glimpse at the puppet behind the shadow play.
S Friend (1994)
Science 265, 334-335
   PDF »
p53 Amino Acids 339-346 Represent the Minimal p53 Repression Domain.
T.-M. Hong, J. J. W. Chen, K. Peck, P.-C. Yang, and C.-W. Wu (2001)
J. Biol. Chem. 276, 1510-1515
   Abstract »    Full Text »    PDF »
NMR Spectroscopy Reveals the Solution Dimerization Interface of p53 Core Domains Bound to Their Consensus DNA.
C. Klein, E. Planker, T. Diercks, H. Kessler, K.-P. Kunkele, K. Lang, S. Hansen, and M. Schwaiger (2001)
J. Biol. Chem. 276, 49020-49027
   Abstract »    Full Text »    PDF »
Peptides from the amino terminal mdm-2-binding domain of p53, designed from conformational analysis, are selectively cytotoxic to transformed cells.
M. Kanovsky, A. Raffo, L. Drew, R. Rosal, T. Do, F. K. Friedman, P. Rubinstein, J. Visser, R. Robinson, P. W. Brandt-Rauf, et al. (2001)
PNAS 98, 12438-12443
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)