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Papillomavirus binding factor (PBF) is an intrinsically disordered protein with potential participation in osteosarcoma genesis, in silico evidence.

Castillo P, Cetina AF, Méndez-Tenorio A, Espinoza-Fonseca LM, Barrón BL - Theor Biol Med Model (2014)

Bottom Line: The physicochemical characteristics determined to PBF, disorder-promoting amino acids, flexibility, hydrophobicity, prediction of secondary and tertiary structures and probability to be crystallized, supported that this protein can be considered as an intrinsically disordered protein (IDP), with a zinc finger-like domain.The in silico analysis to find out PBF interactions with cellular factors, confirmed the experimentally demonstrated interaction of PBF with two key cellular proteins involved in regulation of cellular apoptosis, 14-3-3β and Scythe/BAT3 proteins.Furthermore, other interactions were found with proteins like HDAC1 and TPR which are known to be deregulated in several cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Casco de Santo Tomás, México, DF 11340, México. bbarron@ipn.mx.

ABSTRACT

Background: Papillomavirus binding factor (PBF) or zinc finger protein 395 is a transcription factor associated to a poor prognosis in patients with osteosarcoma, an aggressive bone cancer that predominantly affects adolescents. To investigate the role of the PBF protein in the osteosarcoma genesis, in this paper we present the bioinformatics analysis of physicochemical properties of PBF and its probable interactions with several key cellular targets.

Results: The physicochemical characteristics determined to PBF, disorder-promoting amino acids, flexibility, hydrophobicity, prediction of secondary and tertiary structures and probability to be crystallized, supported that this protein can be considered as an intrinsically disordered protein (IDP), with a zinc finger-like domain. The in silico analysis to find out PBF interactions with cellular factors, confirmed the experimentally demonstrated interaction of PBF with two key cellular proteins involved in regulation of cellular apoptosis, 14-3-3β and Scythe/BAT3 proteins. Furthermore, other interactions were found with proteins like HDAC1 and TPR which are known to be deregulated in several cancers. Experimental confirmation of specific interactions will contribute to understand the osteosarcoma process and might lead to the identification of new targets for diagnosis and treatments.

Conclusions: According to the in silico PBF analyses, this protein can be considered as an IDP capable to bind several key cellular factors, and these interactions might play an important role in the osteosarcoma process.

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Related in: MedlinePlus

PBF tertiary structure predicted with the Robbeta server. A) PBF predicted 3D structure showing long coils in magenta, interrupted by short alpha helices in blue, and beta sheets in red. B) The 3D structure at amino acid residues 216–301, showing the putative zinc finger domain.
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Fig5: PBF tertiary structure predicted with the Robbeta server. A) PBF predicted 3D structure showing long coils in magenta, interrupted by short alpha helices in blue, and beta sheets in red. B) The 3D structure at amino acid residues 216–301, showing the putative zinc finger domain.

Mentions: Due to the fact there is not any report about crystallization of PBF or PBF homologous, we modeled in silico the tertiary PBF protein structure using the Robbeta server. Initially five models were obtained and we chose the model with the best stereochemistry quality, 89.5% of the amino acid residues were located in favoured regions using Procheck (Data not shown). On the other hand, comparison of PBF secondary and tertiary structures showed in both cases an structure formed mainly by long coils or loop structures interrupted by short beta sheets and alpha helixes (Figures 4 and5); and both coincided with the presence of a beta sheet and an alpha helix located among amino acids 216–301 (Figure 5B). Specifically the beta sheet is formed by the amino acids MYKC; while the alpha helix is formed by the amino acids LRSSIVGIKRHVKALH. These sequences were located in the putative zinc finger proposed by Boeckle et al., 2002[2].Figure 4


Papillomavirus binding factor (PBF) is an intrinsically disordered protein with potential participation in osteosarcoma genesis, in silico evidence.

Castillo P, Cetina AF, Méndez-Tenorio A, Espinoza-Fonseca LM, Barrón BL - Theor Biol Med Model (2014)

PBF tertiary structure predicted with the Robbeta server. A) PBF predicted 3D structure showing long coils in magenta, interrupted by short alpha helices in blue, and beta sheets in red. B) The 3D structure at amino acid residues 216–301, showing the putative zinc finger domain.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4265421&req=5

Fig5: PBF tertiary structure predicted with the Robbeta server. A) PBF predicted 3D structure showing long coils in magenta, interrupted by short alpha helices in blue, and beta sheets in red. B) The 3D structure at amino acid residues 216–301, showing the putative zinc finger domain.
Mentions: Due to the fact there is not any report about crystallization of PBF or PBF homologous, we modeled in silico the tertiary PBF protein structure using the Robbeta server. Initially five models were obtained and we chose the model with the best stereochemistry quality, 89.5% of the amino acid residues were located in favoured regions using Procheck (Data not shown). On the other hand, comparison of PBF secondary and tertiary structures showed in both cases an structure formed mainly by long coils or loop structures interrupted by short beta sheets and alpha helixes (Figures 4 and5); and both coincided with the presence of a beta sheet and an alpha helix located among amino acids 216–301 (Figure 5B). Specifically the beta sheet is formed by the amino acids MYKC; while the alpha helix is formed by the amino acids LRSSIVGIKRHVKALH. These sequences were located in the putative zinc finger proposed by Boeckle et al., 2002[2].Figure 4

Bottom Line: The physicochemical characteristics determined to PBF, disorder-promoting amino acids, flexibility, hydrophobicity, prediction of secondary and tertiary structures and probability to be crystallized, supported that this protein can be considered as an intrinsically disordered protein (IDP), with a zinc finger-like domain.The in silico analysis to find out PBF interactions with cellular factors, confirmed the experimentally demonstrated interaction of PBF with two key cellular proteins involved in regulation of cellular apoptosis, 14-3-3β and Scythe/BAT3 proteins.Furthermore, other interactions were found with proteins like HDAC1 and TPR which are known to be deregulated in several cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Casco de Santo Tomás, México, DF 11340, México. bbarron@ipn.mx.

ABSTRACT

Background: Papillomavirus binding factor (PBF) or zinc finger protein 395 is a transcription factor associated to a poor prognosis in patients with osteosarcoma, an aggressive bone cancer that predominantly affects adolescents. To investigate the role of the PBF protein in the osteosarcoma genesis, in this paper we present the bioinformatics analysis of physicochemical properties of PBF and its probable interactions with several key cellular targets.

Results: The physicochemical characteristics determined to PBF, disorder-promoting amino acids, flexibility, hydrophobicity, prediction of secondary and tertiary structures and probability to be crystallized, supported that this protein can be considered as an intrinsically disordered protein (IDP), with a zinc finger-like domain. The in silico analysis to find out PBF interactions with cellular factors, confirmed the experimentally demonstrated interaction of PBF with two key cellular proteins involved in regulation of cellular apoptosis, 14-3-3β and Scythe/BAT3 proteins. Furthermore, other interactions were found with proteins like HDAC1 and TPR which are known to be deregulated in several cancers. Experimental confirmation of specific interactions will contribute to understand the osteosarcoma process and might lead to the identification of new targets for diagnosis and treatments.

Conclusions: According to the in silico PBF analyses, this protein can be considered as an IDP capable to bind several key cellular factors, and these interactions might play an important role in the osteosarcoma process.

Show MeSH
Related in: MedlinePlus