Abstract
The binding of C3b, the opsonic fragment of the third component of complement (C3), to bacterial surface structures mediates two events important in host defence: assembly of the C5b-C9 lytic complex and opsonic recognition by phagocytic cells (for reviews see refs 1, 2). These interactions proceed through a labile binding site3 located on the α′ chain of the C3b molecule, with the resultant formation of a covalent oxy-ester bond4,5 in which the acyl group is contributed by the protein. By exposure of a titratable sulphydryl group6,7 an internal thiolester of native C3 has also been localized to the α′ chain. Studies with 14C-methylamine, a nucleophile which is inherently reactive with a thiolester, have further indicated a stoichiometric (1:1) and covalent interaction, again within the α′ chain8–10. After reaction of the native protein with 14C-methylamine and radioalkylation of the exposed sulphydryl with 3H-iodoacetic acid, a 35-residue tryptic peptide has been isolated that yields the sequence -Cys9-Gly-Glu-Glu12- on Edman degradation; tritium counts are released at step 9 (S[3H]-(carboxymethyl)cysteine) and 14C counts at step 12 (γ-glutamyl[14C]methylamide)8. We now present data which directly demonstrate that the second glutamyl residue of the reactive thiolester can, on proteolytic cleavage of the protein, donate its carbonyl group in a transesterification reaction with appropriate acceptor molecules. These results provide a model for analysis of the interactions at the molecular level between surface constituents of microorganisms and C3b.
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Hostetter, M., Thomas, M., Rosen, F. et al. Binding of C3b proceeds by a transesterification reaction at the thiolester site. Nature 298, 72–75 (1982). https://doi.org/10.1038/298072b0
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DOI: https://doi.org/10.1038/298072b0
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