The internal thioester and the covalent binding properties of the complement proteins C3 and C4

S. K. Alex Law; Alister W. Dodds

doi:10.1002/pro.5560060201

journal article Feb 01, 1997

The internal thioester and the covalent binding properties of the complement proteins C3 and C4

S. K. Alex Law Alister W. Dodds

Protein Science Vol. 6 No. 2 pp. 263-274 · Wiley

View at Publisher Save 10.1002/pro.5560060201

Abstract

AbstractThe covalent binding of complement components C3 and C4 is critical for their activities. This reaction is made possible by the presence of an internal thioester in the native protein. Upon activation, which involves a conformational change initiated by the cleavage of a single peptide bond, the thioester becomes available to react with molecules with nucleophilic groups. This description is probably sufficient to account for the binding of the C4A isotype of human C4 to amino nucleophiles. The binding of the C4B isotype, and most likely C3, to hydroxyl nucleophiles, however, involves a histidine residue, which attacks the thioester to form an intramolecular acyl‐imidazole bond. The released thiolate anion then acts as a base to catalyze the binding of hydroxyl nucleophiles, including water, to the acyl function. This mechanism allows the complement proteins to bind to the hydroxyl groups of carbohydrates found on all biological surfaces, including the components of bacterial cell walls. In addition, the fast hydrolysis of the thioester provides a means to contain this very damaging reaction to the immediate proximity of the site of activation.

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Details

Published: Feb 01, 1997
Vol/Issue: 6(2)
Pages: 263-274
License: View

Authors

Cite This Article

S. K. Alex Law, Alister W. Dodds (1997). The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Science, 6(2), 263-274. https://doi.org/10.1002/pro.5560060201

The internal thioester and the covalent binding properties of the complement proteins C3 and C4

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