Pertactin sandbox1: Difference between revisions
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==Structure and Protein Adhesion Properties== | ==Structure and Protein Adhesion Properties== | ||
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 autotransporter domain located at the N-terminus and a passenger domain located at the C-terminus (“Conserved,” 2015). 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 (Emsley et al., 1996). One of these features is the Arg-Gly-Asp (RGD) tripeptide motif that allows for protein-protein interactions (Emsley et al., 1996). 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 (D’Souza, Ginsberg, & Plow, 1991). Additionally, P.69 contains two proline-rich regions, which are thought to provide important binding sites, and are characteristic of proteins exhibiting binding capabilities (Emsley et al., 1996). Proline is a very unusual amino acid, and its structure limits the possible conformations it can adopt. Especially when chains of proline are bound to each other, the rigidity of these structures allow for reliable binding sites in many different proteins. These regions are typically non-specific, and allow for rapid binding. This is advantageous due to the wide range of ligands that can be bound, increasing the versatility of the proteins that utilize these regions (Williamson, 1994). The linear form of Pertactin that protrudes from the surface of B. pertussis also has a high surface area that could be well suited for targeting mammalian cells (Emsley et al., 1996). Studies have shown that adhesive area strongly affects integrin binding and adhesion strength. The positioning of binding regions also affects adhesion strength, making the combination of these two factors particularly important for proteins that serve this function (Gallant, Michael, & Garcia, 2005). | 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 autotransporter domain located at the N-terminus and a passenger domain located at the C-terminus (“Conserved,” 2015). 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 (Emsley et al., 1996). One of these features is the Arg-Gly-Asp (RGD) tripeptide motif that allows for protein-protein interactions (Emsley et al., 1996). 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 (D’Souza, Ginsberg, & Plow, 1991). Additionally, P.69 contains two proline-rich regions, which are thought to provide important binding sites, and are characteristic of proteins exhibiting binding capabilities (Emsley et al., 1996). Proline is a very unusual amino acid, and its structure limits the possible conformations it can adopt. Especially when chains of proline are bound to each other, the rigidity of these structures allow for reliable binding sites in many different proteins. These regions are typically non-specific, and allow for rapid binding. This is advantageous due to the wide range of ligands that can be bound, increasing the versatility of the proteins that utilize these regions (Williamson, 1994). The linear form of Pertactin that protrudes from the surface of B. pertussis also has a high surface area that could be well suited for targeting mammalian cells (Emsley et al., 1996). Studies have shown that adhesive area strongly affects integrin binding and adhesion strength. The positioning of binding regions also affects adhesion strength, making the combination of these two factors particularly important for proteins that serve this function (Gallant, Michael, & Garcia, 2005). | ||
Revision as of 05:19, 17 November 2015
IntroductionIntroduction
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.
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Structure and Protein Adhesion PropertiesStructure and Protein Adhesion Properties
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 autotransporter domain located at the N-terminus and a passenger domain located at the C-terminus (“Conserved,” 2015). 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 (Emsley et al., 1996). One of these features is the Arg-Gly-Asp (RGD) tripeptide motif that allows for protein-protein interactions (Emsley et al., 1996). 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 (D’Souza, Ginsberg, & Plow, 1991). Additionally, P.69 contains two proline-rich regions, which are thought to provide important binding sites, and are characteristic of proteins exhibiting binding capabilities (Emsley et al., 1996). Proline is a very unusual amino acid, and its structure limits the possible conformations it can adopt. Especially when chains of proline are bound to each other, the rigidity of these structures allow for reliable binding sites in many different proteins. These regions are typically non-specific, and allow for rapid binding. This is advantageous due to the wide range of ligands that can be bound, increasing the versatility of the proteins that utilize these regions (Williamson, 1994). The linear form of Pertactin that protrudes from the surface of B. pertussis also has a high surface area that could be well suited for targeting mammalian cells (Emsley et al., 1996). Studies have shown that adhesive area strongly affects integrin binding and adhesion strength. The positioning of binding regions also affects adhesion strength, making the combination of these two factors particularly important for proteins that serve this function (Gallant, Michael, & Garcia, 2005).
FunctionFunction
DiseaseDisease
RelevanceRelevance
Pertactin vs Pertussis Toxin: Virulence FactorsPertactin vs Pertussis Toxin: Virulence Factors
Pertactin and Pertussis toxin 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 acts as a soluble factor, attacking resident cells of the trachea and lungs such as macrophages (). Pertussis toxin’s wide variety of functions is due to its ability to recognize numerous carbohydrate receptors on eukaryotic cells. Pertussis toxin consists of five different subunits, which most likely is responsible for its ability to recognize multiple receptors (). 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. 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. 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 581st position. Pertactin is involved in binding the bacterial cell to respiratory host cells (). BLAST results 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. This process is responsible for the bacterial cell binding to the host cell. As a whole, Pertactin and Pertussis toxin are structurally very different. 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 (). However, amino acid alignments between Pertactin and each of the five subunits of Pertussis toxin reveals that various sections of Pertactin are the same or highly similar to individual subunits of Pertussis toxin. BLAST results also revealed that subunits 4 and 5’s structures consist of an OB fold and a closed or partly open beta barrel. This may be how Pertactin and Pertussis toxin have similar functions.
Pertactin Function vs Similarly Structured Proteins' FunctionsPertactin Function vs Similarly Structured Proteins' Functions
ReferencesReferences
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.
"Conserved Protein Domain Family." CDD: Conserved Domain Database. NCBI, n.d. Web. 12 Nov. 2015.
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.
Emsley, P., Charles, I., Fairweather, N., & Isaacs, N. (1996). Structure of Bordetella pertussis virulence factor P.69 pertactin. Nature, 90-92.
Gallant, N. D., Michael, K. E., & García, A. J. (2005). Cell Adhesion Strengthening: Contributions of Adhesive Area, Integrin Binding, and Focal Adhesion Assembly. Molecular Biology of the Cell, 16(9), 4329–4340.
Li, L., Dougan, G., Novotny, P., & Charles, I. (n.d.). P.70 pertactin, an outer-membrane protein from Bordetella parapertussis: Cloning, nucleotide sequence and surface expression in Escherichia coli. Molecular Microbiology Mol Microbiol, 409-417.
Williamson, M. P. (1994). The structure and function of proline-rich regions in proteins. Biochemical Journal, 297(Pt 2), 249–260.