HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nagaich, A. K. Articles by Harrington, R. E. Search for Related Content PubMed PubMed Citation Articles by Nagaich, A. K. Articles by Harrington, R. E. Social Bookmarking                      What's this?

Volume 272, Number 23, Issue of June 6, 1997 pp. 14830-14841
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Architectural Accommodation in the Complex of Four p53 DNA Binding Domain Peptides with the p21/waf1/cip1 DNA Response Element

(Received for publication, January 10, 1997, and in revised form, March 25, 1997)

Akhilesh K. Nagaich , Victor B. Zhurkin ^§ , Hiroshi Sakamoto ^¶ , Andrey A. Gorin , G. Marius Clore ^** , Angela M. Gronenborn ^** , Ettore Appella ^¶ and Rodney E. Harrington

From the  Department of Biochemistry/330, School of Medicine, University of Nevada Reno, Reno, Nevada 89557-0014, the  Department of Chemistry, Rutgers University, Piscataway, New Jersey 08855, the ^§ Laboratory of Experimental and Computational Biology and ^¶ Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, and the ^** Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892

High resolution chemical footprinting and cross-linking experiments have provided a basis for elucidating the overall architecture of the complex between the core DNA binding domain of p53 (p53DBD, amino acids 98-309) and the p21/waf1/cip1 DNA response element implicated in the G₁/S phase cell cycle checkpoint. These studies complement both a crystal structure and earlier biophysical studies and provide the first direct experimental evidence that four subunits of p53DBD bind to the response element in a regular staggered array having pseudodyad symmetry. The invariant guanosines in the highly conserved C(A/T)|(T/A)G parts of the consensus half-sites are critical to the p53DBD-DNA binding. Molecular modeling of the complex using the observed peptide-DNA contacts shows that when four subunits of p53DBD bind the response element, the DNA has to bend ~50° to relieve steric clashes among different subunits, consistent with recent DNA cyclization studies. The overall lateral arrangement of the four p53 subunits with respect to the DNA loop comprises a novel nucleoprotein assembly that has not been reported previously in other complexes. We suggest that this kind of nucleoprotein superstructure may be important for p53 binding to response elements packed in chromatin and for subsequent transactivation of p53-mediated genes.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Pan and R. Nussinov Structural Basis for p53 Binding-induced DNA Bending J. Biol. Chem., January 5, 2007; 282(1): 691 - 699. [Abstract] [Full Text] [PDF]

				W. C. Ho, M. X. Fitzgerald, and R. Marmorstein Structure of the p53 Core Domain Dimer Bound to DNA J. Biol. Chem., July 21, 2006; 281(29): 20494 - 20502. [Abstract] [Full Text] [PDF]

				D. B. Veprintsev, S. M. V. Freund, A. Andreeva, S. E. Rutledge, H. Tidow, J. M. Pér. Cañadillas, C. M. Blair, and A. R. Fersht Core domain interactions in full-length p53 in solution PNAS, February 14, 2006; 103(7): 2115 - 2119. [Abstract] [Full Text] [PDF]

				J. Kasparkova, M. Fojta, N. Farrell, and V. Brabec Differential recognition by the tumor suppressor protein p53 of DNA modified by the novel antitumor trinuclear platinum drug BBR3464 and cisplatin Nucleic Acids Res., October 14, 2004; 32(18): 5546 - 5552. [Abstract] [Full Text] [PDF]

				G. Fiucci, S. Beaucourt, D. Duflaut, A. Lespagnol, P. Stumptner-Cuvelette, A. Geant, G. Buchwalter, M. Tuynder, L. Susini, J.-M. Lassalle, et al. Siah-1b is a direct transcriptional target of p53: Identification of the functional p53 responsive element in the siah-1b promoter PNAS, March 9, 2004; 101(10): 3510 - 3515. [Abstract] [Full Text] [PDF]

				K. McKinney and C. Prives Efficient Specific DNA Binding by p53 Requires both Its Central and C-Terminal Domains as Revealed by Studies with High-Mobility Group 1 Protein Mol. Cell. Biol., October 1, 2002; 22(19): 6797 - 6808. [Abstract] [Full Text] [PDF]

				J. Buzek, L. Latonen, S. Kurki, K. Peltonen, and M. Laiho Redox state of tumor suppressor p53 regulates its sequence-specific DNA binding in DNA-damaged cells by cysteine 277 Nucleic Acids Res., June 1, 2002; 30(11): 2340 - 2348. [Abstract] [Full Text] [PDF]

				A. Lebrun, R. Lavery, and H. Weinstein Modeling multi-component protein-DNA complexes: the role of bending and dimerization in the complex of p53 dimers with DNA Protein Eng. Des. Sel., April 1, 2001; 14(4): 233 - 243. [Abstract] [Full Text] [PDF]

				A. L. Okorokov and J. Milner An ATP/ADP-Dependent Molecular Switch Regulates the Stability of p53-DNA Complexes Mol. Cell. Biol., November 1, 1999; 19(11): 7501 - 7510. [Abstract] [Full Text] [PDF]

				A. K. Nagaich, V. B. Zhurkin, S. R. Durell, R. L. Jernigan, E. Appella, and R. E. Harrington p53-induced DNA bending and twisting: p53 tetramer binds on the outer side of a DNA loop and increases DNA twisting PNAS, March 2, 1999; 96(5): 1875 - 1880. [Abstract] [Full Text] [PDF]

				L. Resnick-Silverman, S. St. Clair, M. Maurer, K. Zhao, and J. J. Manfredi Identification of a novel class of genomic DNA-binding sites suggests a mechanism for selectivity in target gene activation by the tumor suppressor protein p53 Genes & Dev., July 15, 1998; 12(14): 2102 - 2107. [Abstract] [Full Text]

				L. Jayaraman, N. C. Moorthy, K. G.K. Murthy, J. L. Manley, M. Bustin, and C. Prives High mobility group protein-1 (HMG-1) is a unique activator of p53 Genes & Dev., February 15, 1998; 12(4): 462 - 472. [Abstract] [Full Text]

				A. K. Nagaich, E. Appella, and R. E. Harrington DNA Bending Is Essential for the Site-specific Recognition of DNA Response Elements by the DNA Binding Domain of the Tumor Suppressor Protein p53 J. Biol. Chem., June 6, 1997; 272(23): 14842 - 14849. [Abstract] [Full Text] [PDF]

				T. Yakovleva, A. Pramanik, T. Kawasaki, K. Tan-No, I. Gileva, H. Lindegren, U. Langel, T. J. Ekstrom, R. Rigler, L. Terenius, et al. p53 Latency. C-TERMINAL DOMAIN PREVENTS BINDING OF p53 CORE TO TARGET BUT NOT TO NONSPECIFIC DNA SEQUENCES J. Biol. Chem., May 4, 2001; 276(19): 15650 - 15658. [Abstract] [Full Text] [PDF]

				C. Klein, G. Georges, K.-P. Kunkele, R. Huber, R. A. Engh, and S. Hansen High Thermostability and Lack of Cooperative DNA Binding Distinguish the p63 Core Domain from the Homologous Tumor Suppressor p53 J. Biol. Chem., September 28, 2001; 276(40): 37390 - 37401. [Abstract] [Full Text] [PDF]

				C. Klein, E. Planker, T. Diercks, H. Kessler, K.-P. Kunkele, K. Lang, S. Hansen, and M. Schwaiger NMR Spectroscopy Reveals the Solution Dimerization Interface of p53 Core Domains Bound to Their Consensus DNA J. Biol. Chem., December 21, 2001; 276(52): 49020 - 49027. [Abstract] [Full Text] [PDF]