Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation

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Papillomaviruses are small DNA tumor viruses that infect mammalian hosts, with consequences from benign to cancerous lesions. The Early protein 2 is the master regulator for the virus life cycle, participating in gene transcription, DNA replication, and viral episome migration. All of these function...

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Autores principales:	Falconi, M., Santolamazza, A., Eliseo, T., De Prat-Gay, G., Cicero, D.O., Desideri, A.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2007
Materias:	Molecular dynamics simulation Papillomavirus Protein flexibility Protein-DNA recognition Transcription factor early protein 2 transcription factor unclassified drug amino acid sequence article carboxy terminal sequence controlled study DNA binding gene targeting Human papillomavirus type 16 molecular dynamics molecular recognition nonhuman nuclear magnetic resonance spectroscopy Papilloma virus priority journal protein DNA binding protein domain protein structure simulation transcription regulation virus strain Animals Bovine papillomavirus 1 Cattle DNA, Viral DNA-Binding Proteins Human papillomavirus 16 Humans Oncogene Proteins, Viral Principal Component Analysis Protein Binding Protein Conformation Protein Structure, Secondary Viral Proteins Bovine papillomavirus Human papillomavirus Mammalia Papillomaviridae
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_1742464X_v274_n9_p2385_Falconi
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paperaa:paper_1742464X_v274_n9_p2385_Falconi2023-06-12T16:50:57Z Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation FEBS J. 2007;274(9):2385-2395 Falconi, M. Santolamazza, A. Eliseo, T. De Prat-Gay, G. Cicero, D.O. Desideri, A. Molecular dynamics simulation Papillomavirus Protein flexibility Protein-DNA recognition Transcription factor early protein 2 transcription factor unclassified drug amino acid sequence article carboxy terminal sequence controlled study DNA binding gene targeting Human papillomavirus type 16 molecular dynamics molecular recognition nonhuman nuclear magnetic resonance spectroscopy Papilloma virus priority journal protein DNA binding protein domain protein structure simulation transcription regulation virus strain Animals Bovine papillomavirus 1 Cattle DNA, Viral DNA-Binding Proteins Human papillomavirus 16 Humans Oncogene Proteins, Viral Principal Component Analysis Protein Binding Protein Conformation Protein Structure, Secondary Viral Proteins Bovine papillomavirus Human papillomavirus Mammalia Papillomaviridae Papillomaviruses are small DNA tumor viruses that infect mammalian hosts, with consequences from benign to cancerous lesions. The Early protein 2 is the master regulator for the virus life cycle, participating in gene transcription, DNA replication, and viral episome migration. All of these functions rely on primary target recognition by its dimeric DNA-binding domain. In this work, we performed molecular dynamics simulations in order to gain insights into the structural dynamics of the DNA-binding domains of two prototypic strains, human papillomavirus strain 16 and the bovine papillomavirus strain 1. The simulations underline different dynamic features in the two proteins. The human papillomavirus strain 16 domain displays a higher flexibility of the β2-β3 connecting loop in comparison with the bovine papillomavirus strain 1 domain, with a consequent effect on the DNA-binding helices, and thus on the modulation of DNA recognition. A compact β-barrel is found in human papillomavirus strain 16, whereas the bovine papillomavirus strain 1 protein is characterized by a loose β-barrel with a large number of cavities filled by water, which provides great flexibility. The rigidity of the human papillomavirus strain 16 β-barrel prevents protein deformation, and, as a consequence, deformable spacers are the preferred targets in complex formation. In contrast, in bovine papillomavirus strain 1, a more deformable β-barrel confers greater adaptability to the protein, allowing the binding of less flexible DNA regions. The flexibility data are confirmed by the experimental NMR S2 values, which are reproduced well by calculation. This feature may provide the protein with an ability to discriminate between spacer sequences. Clearly, the deformability required for the formation of the Early protein 2 C-terminal DNA-binding domain-DNA complexes of various types is based not only on the rigidity of the base sequences in the DNA spacers, but also on the intrinsic deformability properties of each domain. © 2007 The Authors. Fil:De Prat-Gay, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cicero, D.O. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2007 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_1742464X_v274_n9_p2385_Falconi
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	Molecular dynamics simulation Papillomavirus Protein flexibility Protein-DNA recognition Transcription factor early protein 2 transcription factor unclassified drug amino acid sequence article carboxy terminal sequence controlled study DNA binding gene targeting Human papillomavirus type 16 molecular dynamics molecular recognition nonhuman nuclear magnetic resonance spectroscopy Papilloma virus priority journal protein DNA binding protein domain protein structure simulation transcription regulation virus strain Animals Bovine papillomavirus 1 Cattle DNA, Viral DNA-Binding Proteins Human papillomavirus 16 Humans Oncogene Proteins, Viral Principal Component Analysis Protein Binding Protein Conformation Protein Structure, Secondary Viral Proteins Bovine papillomavirus Human papillomavirus Mammalia Papillomaviridae
spellingShingle	Molecular dynamics simulation Papillomavirus Protein flexibility Protein-DNA recognition Transcription factor early protein 2 transcription factor unclassified drug amino acid sequence article carboxy terminal sequence controlled study DNA binding gene targeting Human papillomavirus type 16 molecular dynamics molecular recognition nonhuman nuclear magnetic resonance spectroscopy Papilloma virus priority journal protein DNA binding protein domain protein structure simulation transcription regulation virus strain Animals Bovine papillomavirus 1 Cattle DNA, Viral DNA-Binding Proteins Human papillomavirus 16 Humans Oncogene Proteins, Viral Principal Component Analysis Protein Binding Protein Conformation Protein Structure, Secondary Viral Proteins Bovine papillomavirus Human papillomavirus Mammalia Papillomaviridae Falconi, M. Santolamazza, A. Eliseo, T. De Prat-Gay, G. Cicero, D.O. Desideri, A. Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation
topic_facet	Molecular dynamics simulation Papillomavirus Protein flexibility Protein-DNA recognition Transcription factor early protein 2 transcription factor unclassified drug amino acid sequence article carboxy terminal sequence controlled study DNA binding gene targeting Human papillomavirus type 16 molecular dynamics molecular recognition nonhuman nuclear magnetic resonance spectroscopy Papilloma virus priority journal protein DNA binding protein domain protein structure simulation transcription regulation virus strain Animals Bovine papillomavirus 1 Cattle DNA, Viral DNA-Binding Proteins Human papillomavirus 16 Humans Oncogene Proteins, Viral Principal Component Analysis Protein Binding Protein Conformation Protein Structure, Secondary Viral Proteins Bovine papillomavirus Human papillomavirus Mammalia Papillomaviridae
description	Papillomaviruses are small DNA tumor viruses that infect mammalian hosts, with consequences from benign to cancerous lesions. The Early protein 2 is the master regulator for the virus life cycle, participating in gene transcription, DNA replication, and viral episome migration. All of these functions rely on primary target recognition by its dimeric DNA-binding domain. In this work, we performed molecular dynamics simulations in order to gain insights into the structural dynamics of the DNA-binding domains of two prototypic strains, human papillomavirus strain 16 and the bovine papillomavirus strain 1. The simulations underline different dynamic features in the two proteins. The human papillomavirus strain 16 domain displays a higher flexibility of the β2-β3 connecting loop in comparison with the bovine papillomavirus strain 1 domain, with a consequent effect on the DNA-binding helices, and thus on the modulation of DNA recognition. A compact β-barrel is found in human papillomavirus strain 16, whereas the bovine papillomavirus strain 1 protein is characterized by a loose β-barrel with a large number of cavities filled by water, which provides great flexibility. The rigidity of the human papillomavirus strain 16 β-barrel prevents protein deformation, and, as a consequence, deformable spacers are the preferred targets in complex formation. In contrast, in bovine papillomavirus strain 1, a more deformable β-barrel confers greater adaptability to the protein, allowing the binding of less flexible DNA regions. The flexibility data are confirmed by the experimental NMR S2 values, which are reproduced well by calculation. This feature may provide the protein with an ability to discriminate between spacer sequences. Clearly, the deformability required for the formation of the Early protein 2 C-terminal DNA-binding domain-DNA complexes of various types is based not only on the rigidity of the base sequences in the DNA spacers, but also on the intrinsic deformability properties of each domain. © 2007 The Authors.
format	Artículo Artículo publishedVersion
author	Falconi, M. Santolamazza, A. Eliseo, T. De Prat-Gay, G. Cicero, D.O. Desideri, A.
author_facet	Falconi, M. Santolamazza, A. Eliseo, T. De Prat-Gay, G. Cicero, D.O. Desideri, A.
author_sort	Falconi, M.
title	Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation
title_short	Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation
title_full	Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation
title_fullStr	Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation
title_full_unstemmed	Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation
title_sort	molecular dynamics of the dna-binding domain of the papillomavirus e2 transcriptional regulator uncover differential properties for dna target accommodation
publishDate	2007
url	http://hdl.handle.net/20.500.12110/paper_1742464X_v274_n9_p2385_Falconi
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Molecular dynamics of the DNA-binding domain of the papillomavirus E2 transcriptional regulator uncover differential properties for DNA target accommodation

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