Sandbox 300: Difference between revisions
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The structural details of protein A were solved by the nuclear magnetic resonance method. The length of the amino acid chain of protein A contains 508 residues. The amino acids cystein and tryptophan do not occur in the amino acid sequence. The molecular weight of the described protein is 55439 Dalton and it consists of only one protein chain. | The structural details of protein A were solved by the nuclear magnetic resonance method. The length of the amino acid chain of protein A contains 508 residues. The amino acids cystein and tryptophan do not occur in the amino acid sequence. The molecular weight of the described protein is 55439 Dalton and it consists of only one protein chain. | ||
The 3D structure is build up of three α-helixes and it consists of five extracellular domains, which are designated as E, D, A, B and C. Furthermore the protein contains cell-wall spanning regions, called X'''r''' and X'''c''', and a hydrophobic membrane spanning domain, which is distal to LPXTG and consists of 18-20 residues<ref>Hartleib, J., Köhler, N., Dickinson, R. B., Chhatwal, G. S., Sixma, J. J., M, O., Foster, T. J., et al. ( | The 3D structure is build up of three α-helixes and it consists of five extracellular domains, which are designated as E, D, A, B and C. Furthermore the protein contains cell-wall spanning regions, called X'''r''' and X'''c''', and a hydrophobic membrane spanning domain, which is distal to LPXTG and consists of 18-20 residues<ref>Hartleib, J., Köhler, N., Dickinson, R. B., Chhatwal, G. S., Sixma, J. J., M, O., Foster, T. J., et al. (2000). Protein A is the von Willebrand factor binding protein on Staphylococcus aureus, 2149-2156</ref>. Protein A exists in a secreted and a cell wall anchored form. If it is bound to the cell wall of Staphylococcus aureus it is covalently linked to the peptidoglycan via its C-terminal domain. | ||
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The domains D and E of protein A are able to bind to the Fab fragments of immunoglobulins through variable (V) regions. The Fv-binding sites enable protein A to cross-link membrane IgM on B cells and therefore mediate the activation of these cells, which confers a superantigen function to protein A. Several features of the interactions of protein A with host B lymphocytes are similar to those of superantigens for T lymphocytes, which can cause various inflammatory diseases, such as toxic shock syndrome and food poisoning. | The domains D and E of protein A are able to bind to the Fab fragments of immunoglobulins through variable (V) regions. The Fv-binding sites enable protein A to cross-link membrane IgM on B cells and therefore mediate the activation of these cells, which confers a superantigen function to protein A. Several features of the interactions of protein A with host B lymphocytes are similar to those of superantigens for T lymphocytes, which can cause various inflammatory diseases, such as toxic shock syndrome and food poisoning. | ||
Furthermore it was shown that the staphylococcal protein A is able to activate the classical complement pathway. This activation depends on the binding of a VH3+ IgM molecule to protein A, which results in the generation of an inflammatory reaction. The protein A induced complement activation is another factor, which contributes to the staphylococcal virulence. | Furthermore it was shown that the staphylococcal protein A is able to activate the classical complement pathway. This activation depends on the binding of a VH3+ IgM molecule to protein A, which results in the generation of an inflammatory reaction. The protein A induced complement activation is another factor, which contributes to the staphylococcal virulence. | ||
Moreover, invasive Staphylococcus aureus disease are often associated with the complication of endovascular infections. In order to cause this kind of complication staphylococci must first adhere to endovascular foci and colonize these tissues. One of the factors released by endothelial cells and by platelets is the von Willbrrand factor (vWF). This factor mediates the adhesion of platelets at damaged endothelial sites. It was shown that vWF binds to and also promotes the adhesion of staphylococcal cells to vWF-absorbed surfaces. It could also be demonstrated that the recognition of vWF is mediated by the staphylococcal protein A | Moreover, invasive Staphylococcus aureus disease are often associated with the complication of endovascular infections. In order to cause this kind of complication staphylococci must first adhere to endovascular foci and colonize these tissues. One of the factors released by endothelial cells and by platelets is the von Willbrrand factor (vWF). This factor mediates the adhesion of platelets at damaged endothelial sites. It was shown that vWF binds to and also promotes the adhesion of staphylococcal cells to vWF-absorbed surfaces. It could also be demonstrated that the recognition of vWF is mediated by the staphylococcal protein A<ref>Hartleib, J., Köhler, N., Dickinson, R. B., Chhatwal, G. S., Sixma, J. J., M, O., Foster, T. J., et al. (2000). Protein A is the von Willebrand factor binding protein on Staphylococcus aureus, 2149-2156</ref>. | ||
Protein A defective mutants have shown reduced virulence in murine models. These observations can be explained most likely by the antiphagocytic effect of protein A binding IgG Fc fragments. | Protein A defective mutants have shown reduced virulence in murine models. These observations can be explained most likely by the antiphagocytic effect of protein A binding IgG Fc fragments<ref>Hartleib, J., Köhler, N., Dickinson, R. B., Chhatwal, G. S., Sixma, J. J., M, O., Foster, T. J., et al. (2000). Protein A is the von Willebrand factor binding protein on Staphylococcus aureus, 2149-2156</ref>. | ||
==Medical implication== | ==Medical implication== | ||