Complement activation and antibody binding by pneumolysin via a region of the toxin homologous to a human acute-phase protein.
Pneumolysin, a membrane-damaging toxin, is known to activate the classical complement pathway. We have shown that 1 microgram ml-1 of pneumolysin can activate complement, which is a much lower level than observed previously. We have identified two distinct regions of pneumolysin which show homology with a contiguous sequence within acute-phase proteins, including human C-reactive protein (CRP). Site-directed mutagenesis of the pneumolysin gene was used to change residues common to pneumolysin and CRP. Some of the modified toxins had a reduced ability both to activate complement and bind antibody. We suggest that the ability of pneumolysin to activate complement is related to its ability to bind the Fc portion of immunoglobulin G.
Mitchell
T J
TJ
Department of Microbiology, University of Leicester, UK.
Andrew
P W
PW
Saunders
F K
FK
Smith
A N
AN
Boulnois
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins; D002097:C-Reactive Protein / Q000737:chemistry*; D003167:Complement Activation / Q000276:immunology*; D003603:Cytotoxins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011817:Rabbits; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D013296:Streptococcus pneumoniae / Q000378:metabolism; D013301:Streptolysins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D001426:Bacterial Proteins; D003603:Cytotoxins; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D002097:C-Reactive Protein