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Science 4 June 1999:
Vol. 284. no. 5420, pp. 1673 - 1677
DOI: 10.1126/science.284.5420.1673
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Reports

Crystal Structure of the Human Papillomavirus Type 18 E2 Activation Domain

Seth F. Harris, Michael R. Botchan *

The papillomavirus E2 protein regulates viral transcription and DNA replication through interactions with cellular and viral proteins. The amino-terminal activation domain, which represents a protein class whose structural themes are poorly understood, contains key residues that mediate these functional contacts. The crystal structure of a protease-resistant core of the human papillomavirus type 18 E2 activation domain reveals a novel fold creating a cashew-shaped form with a glutamine-rich alpha  helix packed against a beta -sheet framework. The protein surface shows extensive overlap of determinants for replication and transcription. The structure broadens the concept of activators to include proteins with potentially malleable, but certainly ordered, structures.

Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.
*   To whom correspondence should be addressed. E-mail: mbotchan{at}uclink4.berkeley.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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E. E. Hernandez-Ramon, J. E. Burns, W. Zhang, H. F. Walker, S. Allen, A. A. Antson, and N. J. Maitland (2008)
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The recognition of local DNA conformation by the human papillomavirus type 6 E2 protein.
E. Hooley, V. Fairweather, A. R. Clarke, K. Gaston, and R. Leo Brady (2006)
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Bromodomain Protein 4 Mediates the Papillomavirus E2 Transcriptional Activation Function.
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J. Virol. 80, 4276-4285
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Conditional Mutations in the Mitotic Chromosome Binding Function of the Bovine Papillomavirus Type 1 E2 Protein.
P.-S. Zheng, J. Brokaw, and A. A. McBride (2005)
J. Virol. 79, 1500-1509
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Positive Contribution of Hydration on DNA Binding by E2c Protein from Papillomavirus.
L. M. T. R. Lima and J. L. Silva (2004)
J. Biol. Chem. 279, 47968-47974
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The X-ray structure of the papillomavirus helicase in complex with its molecular matchmaker E2.
E. A. Abbate, J. M. Berger, and M. R. Botchan (2004)
Genes & Dev. 18, 1981-1996
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Pathogenesis of Human Papillomaviruses in Differentiating Epithelia.
M. S. Longworth and L. A. Laimins (2004)
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Hepatitis C Virus Quasispecies Variability Modulates Nonstructural Protein 5A Transcriptional Activation, Pointing to Cellular Compartmentalization of Virus-Host Interactions.
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Crystal Structure of the E2 Transactivation Domain of Human Papillomavirus Type 11 Bound to a Protein Interaction Inhibitor.
Y. Wang, R. Coulombe, D. R. Cameron, L. Thauvette, M.-J. Massariol, L. M. Amon, D. Fink, S. Titolo, E. Welchner, C. Yoakim, et al. (2004)
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Analysis of Chromatin Attachment and Partitioning Functions of Bovine Papillomavirus Type 1 E2 Protein.
A. Abroi, I. Ilves, S. Kivi, and M. Ustav (2004)
J. Virol. 78, 2100-2113
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From The Cover: Automated protein crystal structure determination using ELVES.
J. Holton and T. Alber (2004)
PNAS 101, 1537-1542
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A Transactivator Function of Cottontail Rabbit Papillomavirus E2 Is Essential for Tumor Induction in Rabbits.
S. Jeckel, E. Huber, F. Stubenrauch, and T. Iftner (2002)
J. Virol. 76, 11209-11215
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Stability of the Human Papillomavirus Type 18 E2 Protein Is Regulated by a Proteasome Degradation Pathway through Its Amino-Terminal Transactivation Domain.
S. Bellanger, C. Demeret, S. Goyat, and F. Thierry (2001)
J. Virol. 75, 7244-7251
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DNA tightens the dimeric DNA-binding domain of human papillomavirus E2 protein without changes in volume.
L. M. T. R. Lima, D. Foguel, and J. L. Silva (2000)
PNAS
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AMF-1/Gps2 Binds p300 and Enhances Its Interaction with Papillomavirus E2 Proteins.
Y.-C. Peng, D. E. Breiding, F. Sverdrup, J. Richard, and E. J. Androphy (2000)
J. Virol. 74, 5872-5879
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The Hinge of the Human Papillomavirus Type 11 E2 Protein Contains Major Determinants for Nuclear Localization and Nuclear Matrix Association.
N. Zou, B. Y. Lin, F. Duan, K.-Y. Lee, G. Jin, R. Guan, G. Yao, E. J. Lefkowitz, T. R. Broker, and L. T. Chow (2000)
J. Virol. 74, 3761-3770
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cAMP Response Element-binding Protein-binding Protein Binds to Human Papillomavirus E2 Protein and Activates E2-dependent Transcription.
D. Lee, B. Lee, J. Kim, D. W. Kim, and J. Choe (2000)
J. Biol. Chem. 275, 7045-7051
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The Multifunctional Character of a Geminivirus Replication Protein Is Reflected by Its Complex Oligomerization Properties.
B. M. Orozco, L.-J. Kong, L. A. Batts, S. Elledge, and L. Hanley-Bowdoin (2000)
J. Biol. Chem. 275, 6114-6122
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Two Patches of Amino Acids on the E2 DNA Binding Domain Define the Surface for Interaction with E1.
G. Chen and A. Stenlund (2000)
J. Virol. 74, 1506-1512
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High and Low Levels of Cottontail Rabbit Papillomavirus E2 Protein Generate Opposite Effects on Gene Expression.
T. Fujii, J. L. Brandsma, X. Peng, S. Srimatkandada, L. Li, A. Canaan, and A. B. Deisseroth (2001)
J. Biol. Chem. 276, 867-874
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DNA tightens the dimeric DNA-binding domain of human papillomavirus E2 protein without changes in volume.
L. M. T. R. Lima, D. Foguel, and J. L. Silva (2000)
PNAS 97, 14289-14294
   Abstract »    Full Text »    PDF »


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