P.69 Pertactin Structure and Function: Difference between revisions
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Pertactin is a single unit protein consisting of a 16-stranded parallel beta-helix with a v-shaped cross section. There are two conserved domains within Pertactin, an auto transporter domain located at the N-terminus and a passenger domain located at the C-terminus <ref name= "CON">"Conserved Protein Domain Family." CDD: Conserved Domain Database. NCBI, n.d. Web. 12 Nov. 2015.</ref>. | Pertactin is a single unit protein consisting of a 16-stranded parallel beta-helix with a v-shaped cross section. There are two conserved domains within Pertactin, an auto transporter domain located at the N-terminus and a passenger domain located at the C-terminus <ref name= "CON">"Conserved Protein Domain Family." CDD: Conserved Domain Database. NCBI, n.d. Web. 12 Nov. 2015.</ref>. | ||
Pathogens such as ''Bordetella pertussis'' and ''Bordetella parapertussis'' utilize virulence factors to adhere to target cells, which contribute to the overall pathogenicity of the organism. Pertactin shares homology with other proteins that are known to aid in cell-cell adhesion, emphasizing the importance of structure and how it relates to function. P.69 pertactin has been shown to adhere to mammalian cells, and has several features that contribute to this functionality <ref name="EMS">Emsley, P., Charles, I., Fairweather, N., & Isaacs, N. (1996). Structure of Bordetella pertussis virulence factor P.69 pertactin. Nature, 90-92.</ref>. | Pathogens such as ''Bordetella pertussis'' and ''Bordetella parapertussis'' utilize virulence factors to adhere to target cells, which contribute to the overall pathogenicity of the organism. Pertactin shares homology with other proteins that are known to aid in cell-cell adhesion, emphasizing the importance of structure and how it relates to function. P.69 pertactin has been shown to adhere to mammalian cells, and has several features that contribute to this functionality <ref name="EMS">Emsley, P., Charles, I., Fairweather, N., & Isaacs, N. (1996). Structure of ''Bordetella pertussis'' virulence factor P.69 pertactin. Nature, 90-92.</ref>. | ||
One of these features is the <scene name='71/716564/Arg_gly_asp/1'>Arg-Gly-Asp (RGD) tripeptide motif</scene> that allows for protein-protein interactions <ref name="EMS" />. This motif has been found in several proteins, and has been shown to support cell adhesion in most cases. A subset of cell-surface proteins, called integrins, act as receptors for cell adhesion molecules. These integrins recognize the RGD motif within their ligands, and allow for cell-substratum and cell-cell interactions <ref>D'Souza, S. E., Ginsberg, M. H., & Plow, E. F. (1991). Arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif. Trends In Biochemical Sciences, 16(7), 246-250.</ref>. | One of these features is the <scene name='71/716564/Arg_gly_asp/1'>Arg-Gly-Asp (RGD) tripeptide motif</scene> that allows for protein-protein interactions <ref name="EMS" />. This motif has been found in several proteins, and has been shown to support cell adhesion in most cases. A subset of cell-surface proteins, called integrins, act as receptors for cell adhesion molecules. These integrins recognize the RGD motif within their ligands, and allow for cell-substratum and cell-cell interactions <ref>D'Souza, S. E., Ginsberg, M. H., & Plow, E. F. (1991). Arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif. Trends In Biochemical Sciences, 16(7), 246-250.</ref>. | ||
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== Relevance== | == Relevance== | ||
P.69 has recently been shown to be an agglutinogen, an antigen that produces agglutinin which causes particles to coagulate <ref>Charles, I. G., Dougan, G., Pickard, D., Chatfield, S., Smith, M., Novotny, P., … Fairweather, N. F. (1989). Molecular cloning and characterization of protective outer membrane protein P.69 from Bordetella pertussis. Proceedings of the National Academy of Sciences of the United States of America, 86(10), 3554–3558.</ref>. Due to agglutinogen properties as well as the ability to kill ''B. pertussis'', P.69 has the potential for use in an acellular vaccine as an antigen for whooping cough <ref>Gotto, J. W., Eckhardt, T., Reilly, P. A., Scott, J. V., Cowell, J. L., Metcalf, T. N., … Siegel, M. (1993). Biochemical and immunological properties of two forms of pertactin, the 69,000-molecular-weight outer membrane protein of Bordetella pertussis. Infection and Immunity, 61(5), 2211–2215.</ref>. Specifically, region 1 of pertactin has been found to be responsible for immunity properties due to its polymorphic attributes <ref>King A, Berbers G, van Oirschot H, Hoogerhout P, Knipping K, Mooi F (2001). Microbiology 147(11):2885-2895 doi:10.1099/00221287-147-11-2885. | P.69 has recently been shown to be an agglutinogen, an antigen that produces agglutinin which causes particles to coagulate <ref>Charles, I. G., Dougan, G., Pickard, D., Chatfield, S., Smith, M., Novotny, P., … Fairweather, N. F. (1989). Molecular cloning and characterization of protective outer membrane protein P.69 from ''Bordetella pertussis''. Proceedings of the National Academy of Sciences of the United States of America, 86(10), 3554–3558.</ref>. Due to agglutinogen properties as well as the ability to kill ''B. pertussis'', P.69 has the potential for use in an acellular vaccine as an antigen for whooping cough <ref>Gotto, J. W., Eckhardt, T., Reilly, P. A., Scott, J. V., Cowell, J. L., Metcalf, T. N., … Siegel, M. (1993). Biochemical and immunological properties of two forms of pertactin, the 69,000-molecular-weight outer membrane protein of ''Bordetella pertussis''. Infection and Immunity, 61(5), 2211–2215.</ref>. Specifically, region 1 of pertactin has been found to be responsible for immunity properties due to its polymorphic attributes <ref>King A, Berbers G, van Oirschot H, Hoogerhout P, Knipping K, Mooi F (2001). Microbiology 147(11):2885-2895 doi:10.1099/00221287-147-11-2885. | ||
</ref>. | </ref>. | ||
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[[Image:Prn6.png]] | [[Image:Prn6.png]] | ||
Pertactin and #REDIRECT [[Pertussis Toxin ATP-Complex]] are both virulence factors that contribute to respiratory tract infection and whooping cough. Both are responsible for binding the foreign bacterial cell to the host organism’s cells. Despite similar functions, Pertactin and Pertussis toxin have very different structures. Pertussis toxin is a virulence factor only produced by Bordetella pertussis. It is known to cause systemic symptoms of pertussis disease, such as leukocytosis and histamine sensitivity. It has also, recently, been discovered to promote respiratory infection by inhibiting and modulating host cell immune responses. Pertussis toxin promotes infection by acting as a soluble factor, which attacks resident cells of the trachea and lungs, such as macrophages<ref name= "Car">Carbonetti, Nicholas H. “Pertussis Toxin and Adenylate Cyclase Toxin: Key Virulence Factors of Bordetella Pertussis and Cell Biology Tools.” Future microbiology 5 (2010): 455–469. PMC. Web. 17 Nov. 2015.</ref>. Pertactin is also a virulence factor known to contribute to whooping cough. Pertactin is found in Bordetella pampertussis, and a 91.3% homologous protein is found in Bordetella pertussis, the species which produces Pertussis toxin. An amino acid alignment between the two strains reveals that the proteins differ in the number of repeated sequences. B. pampertussis has a series of approximately twenty more amino acids beginning at the 580th position ([[Media:Prn6.png| Figure 6]]). Similarly to Pertussis toxin, Pertactin is involved in binding the bacterial cell to respiratory host cells, however, less is known about the specific cells Pertactin binds to in order to promote infection.<ref name="CON" /> | Pertactin and #REDIRECT [[Pertussis Toxin ATP-Complex]] are both virulence factors that contribute to respiratory tract infection and whooping cough. Both are responsible for binding the foreign bacterial cell to the host organism’s cells. Despite similar functions, Pertactin and Pertussis toxin have very different structures. Pertussis toxin is a virulence factor only produced by ''Bordetella pertussis''. It is known to cause systemic symptoms of pertussis disease, such as leukocytosis and histamine sensitivity. It has also, recently, been discovered to promote respiratory infection by inhibiting and modulating host cell immune responses. Pertussis toxin promotes infection by acting as a soluble factor, which attacks resident cells of the trachea and lungs, such as macrophages<ref name= "Car">Carbonetti, Nicholas H. “Pertussis Toxin and Adenylate Cyclase Toxin: Key Virulence Factors of Bordetella Pertussis and Cell Biology Tools.” Future microbiology 5 (2010): 455–469. PMC. Web. 17 Nov. 2015.</ref>. Pertactin is also a virulence factor known to contribute to whooping cough. Pertactin is found in ''Bordetella pampertussis'', and a 91.3% homologous protein is found in ''Bordetella pertussis'', the species which produces Pertussis toxin. An amino acid alignment between the two strains reveals that the proteins differ in the number of repeated sequences. ''B. pampertussis'' has a series of approximately twenty more amino acids beginning at the 580th position ([[Media:Prn6.png| Figure 6]]). Similarly to Pertussis toxin, Pertactin is involved in binding the bacterial cell to respiratory host cells, however, less is known about the specific cells Pertactin binds to in order to promote infection.<ref name="CON" /> | ||
Despite similar functions, Pertussis toxin and Pertactin have very different structures. As mentioned previously, Pertactin’s structure consists of a 16-stranded parallel beta-helix with a v-shaped cross section, while Pertussis toxin consists of five subunits.<ref name="CON" />BLAST results of Pertactin revealed that two domains, autotransporter and PL1_Passenger_AT, are conserved. The autotransporter domain is located at the C-terminus of Pertactin and functions to transport the passenger domain, located at the N-terminus of Pertactin, in to the host cell, where the two domains are typically cleaved.<ref name="CON" /> This process is responsible for the bacterial cell binding to the host cell. While Pertactin is a single polypeptide chain, Pertussis toxin consists of five different subunits: S1 makes up subunit A and subunit B is a pentameric ring made of S2, S3, two S4 and S5. BLAST results revealed that a single domain is contained within subunits 1, 4 and 5: Pertussis_S1 superfamily, Pertussis_S4 superfamily and Pertussis_S5 superfamily. Subunits 2 and 3 contain an ATP superfamily and Pertussis_S2S3 Superfamily, which represent the N-terminal domain of aerolysin and pertussis toxin and the C-terminal domain, respectively. The individual structures may be responsible for Pertussis toxin’s ability to recognize receptors on numerous cell types<ref name="Car" />. | Despite similar functions, Pertussis toxin and Pertactin have very different structures. As mentioned previously, Pertactin’s structure consists of a 16-stranded parallel beta-helix with a v-shaped cross section, while Pertussis toxin consists of five subunits.<ref name="CON" />BLAST results of Pertactin revealed that two domains, autotransporter and PL1_Passenger_AT, are conserved. The autotransporter domain is located at the C-terminus of Pertactin and functions to transport the passenger domain, located at the N-terminus of Pertactin, in to the host cell, where the two domains are typically cleaved.<ref name="CON" /> This process is responsible for the bacterial cell binding to the host cell. While Pertactin is a single polypeptide chain, Pertussis toxin consists of five different subunits: S1 makes up subunit A and subunit B is a pentameric ring made of S2, S3, two S4 and S5. BLAST results revealed that a single domain is contained within subunits 1, 4 and 5: Pertussis_S1 superfamily, Pertussis_S4 superfamily and Pertussis_S5 superfamily. Subunits 2 and 3 contain an ATP superfamily and Pertussis_S2S3 Superfamily, which represent the N-terminal domain of aerolysin and pertussis toxin and the C-terminal domain, respectively. The individual structures may be responsible for Pertussis toxin’s ability to recognize receptors on numerous cell types<ref name="Car" />. | ||