PMID:15585873
| Citation |
McDowell, JV, Wolfgang, J, Senty, L, Sundy, CM, Noto, MJ and Marconi, RT (2004) Demonstration of the involvement of outer surface protein E coiled coil structural domains and higher order structural elements in the binding of infection-induced antibody and the complement-regulatory protein, factor H. J. Immunol. 173:7471-80 |
|---|---|
| Abstract |
Factor H (fH) is an important regulator of the alternative complement cascade. Several human pathogens have been shown to bind fH to their surface, a process that facilitates immune evasion or cell to cell interaction. Among the pathogens that bind fH are some Borrelia species associated with Lyme disease and relapsing fever. The fH-binding proteins of the Lyme spirochetes form two classes (I and II). In Borrelia burgdorferi B31MI, class I includes the outer surface protein E (OspE) paralogs, L39, N38, and P38, whereas the class II group includes A68 and additional proteins that have not yet been identified. To identify the OspE determinants involved in fH and OspE-targeting infection-induced Ab (iAb) binding, deletion, random, and site-directed mutagenesis of L39 were performed. Mutations in several different regions of L39 abolished fH and or iAb binding, indicating that separable domains and residues of OspE are required for ligand binding. Some of the mutants that lost the ability to bind fH, iAb, or both had only a single amino acid change. Site-directed mutagenesis of three putative coiled coil motifs of OspE revealed that these higher order structures are required for fH binding but not for iAb binding. The data presented within demonstrate that the binding of fH and iAb to the OspE protein is mediated by higher order structures and protein conformation. These studies advance our understanding of fH binding as a virulence mechanism and facilitate ongoing efforts to use fH-binding proteins in the development of microbial vaccines. |
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| Keywords |
Amino Acid Motifs/genetics; Amino Acid Sequence; Amino Acid Substitution/genetics; Amino Acid Substitution/immunology; Antibodies, Bacterial/biosynthesis; Antibodies, Bacterial/metabolism; Antigens, Bacterial/chemistry; Antigens, Bacterial/genetics; Antigens, Bacterial/immunology; Antigens, Bacterial/physiology; Bacterial Outer Membrane Proteins/chemistry; Bacterial Outer Membrane Proteins/genetics; Bacterial Outer Membrane Proteins/immunology; Bacterial Outer Membrane Proteins/physiology; Bacterial Proteins/chemistry; Bacterial Proteins/genetics; Bacterial Proteins/immunology; Bacterial Proteins/physiology; Binding Sites, Antibody/genetics; Borrelia/genetics; Borrelia/immunology; Borrelia/pathogenicity; Complement Factor H/antagonists & inhibitors; Complement Factor H/metabolism; DNA Mutational Analysis; Lipoproteins/chemistry; Lipoproteins/genetics; Lipoproteins/immunology; Lipoproteins/physiology; Lyme Disease/immunology; Lyme Disease/metabolism; Lyme Disease/microbiology; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Binding/genetics; Protein Binding/immunology; Protein Structure, Secondary/genetics; Protein Structure, Tertiary/genetics; Sequence Deletion/immunology |
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