Pertactin sandbox1: Difference between revisions
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==Introduction== | ==Introduction== | ||
Pertactin is a virulence toxin of ''Bordetella parapertussis'' and close relatives, such as ''Bordetella pertussis''. It is an outer surface membrane protein involved in the binding of ''B. parapertussis'' to host cells, which aids the bacteria in infection of host cells with whooping cough. | Pertactin is a virulence toxin of ''Bordetella parapertussis'' and close relatives, such as ''Bordetella pertussis''. It is an outer surface membrane protein involved in the binding of ''B. parapertussis'' to host cells, which aids the bacteria in infection of host cells with whooping cough. Many of the conserved regions in this protein, such as its passenger and autotransporter domains, contribute directly to the overall virulence and pathogenicity of these organisms. | ||
Autotransporters make up the largest protein family in Gram-negative bacteria. They are usually comprised of a C-terminal beta-barrel-shaped transporter domain anchored in the outer membrane and an N-terminal passenger domain that crosses the outer membrane through the beta barrel (Figure 1a). The autotransporter is considered a virulence factor with the passenger domain contributing to the virulence of the pathogen. This N-terminal domain is similar in structure between different species, but the functions vary greatly. However, the C-terminal beta-barrel domain is a highly conserved structure for transport across the membrane but can vary greatly in the sequence. Many factors including biogenesis, use of accessory proteins, and fate of the beta-barrel translocator are not well known. | Autotransporters make up the largest protein family in Gram-negative bacteria. They are usually comprised of a C-terminal beta-barrel-shaped transporter domain anchored in the outer membrane and an N-terminal passenger domain that crosses the outer membrane through the beta barrel (Figure 1a). The autotransporter is considered a virulence factor with the passenger domain contributing to the virulence of the pathogen. This N-terminal domain is similar in structure between different species, but the functions vary greatly. However, the C-terminal beta-barrel domain is a highly conserved structure for transport across the membrane but can vary greatly in the sequence. Many factors including biogenesis, use of accessory proteins, and fate of the beta-barrel translocator are not well known. | ||
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Regardless if pertactin functions as an adhesion molecule, it is very biologically relevant. Pertactin would make for a good vaccine candidate. Manipulation of the passenger domain can be performed so that a gene for a certain protein from a different species can be inserted in the passenger domain thus replacing the wild type passenger domain <ref name="BEN" />. This would make for a very good vaccine candidate. Not only would the translocator of ''B. pertussis'' can be recognized as an antigen by the host as well as the heterologous protein inserted in the passenger domain. This could be the basis for a heterologous vaccine (combating two species). | Regardless if pertactin functions as an adhesion molecule, it is very biologically relevant. Pertactin would make for a good vaccine candidate. Manipulation of the passenger domain can be performed so that a gene for a certain protein from a different species can be inserted in the passenger domain thus replacing the wild type passenger domain <ref name="BEN" />. This would make for a very good vaccine candidate. Not only would the translocator of ''B. pertussis'' can be recognized as an antigen by the host as well as the heterologous protein inserted in the passenger domain. This could be the basis for a heterologous vaccine (combating two species). | ||
The last step of secretion in autotransporters is C→ N terminal threading of the passenger domain through the outer membrane-spanning portion of the protein. After this step, the original structure of pertactin is formed. Interestingly, this translocation process does not depend on the consumption of ATP nor the presence of a proton gradient <ref>Junker, M., Schuster, C. C., McDonnell, A. V., Sorg, K. A., Finn, M. C., Berger, B., & Clark, P. L. (2006). Pertactin β-helix folding mechanism suggests common themes for the secretion and folding of autotransporter proteins. Proceedings of the National Academy of Sciences of the United States of America, 103(13), 4918–4923.</ref>. | The last step of secretion in autotransporters is C→ N terminal threading of the passenger domain through the outer membrane-spanning portion of the protein. After this step, the original structure of pertactin is formed. Interestingly, this translocation process does not depend on the consumption of ATP nor the presence of a proton gradient <ref>Junker, M., Schuster, C. C., McDonnell, A. V., Sorg, K. A., Finn, M. C., Berger, B., & Clark, P. L. (2006). Pertactin β-helix folding mechanism suggests common themes for the secretion and folding of autotransporter proteins. Proceedings of the National Academy of Sciences of the United States of America, 103(13), 4918–4923.</ref>. | ||
== 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>. | ||