A statistical model for activation of Factor C by binding to LPS aggregates
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Published data on Factor C activity at various LPS and Lipid A concentrations (Nakamura et al. in Eur J Biochem 176:89, 1988; Kobayashi et al. in J Biol Chem 37:25987, 2014) were rearranged to show that Factor C exhibited its maximum activity at a specific concentration of LPS. A statistical model was proposed for examining whether a single LPS molecule binding activates Factor C (monomeric activation) or dimerization of Factor C is necessary for the activation (dimeric activation). In the monomeric activation model the plots of the relative activity of Factor C against the molar ratio of LPS to Factor C were different from those in the published data. The plots in the dimeric activation model lie on a bell-shaped curve, whatever the Factor C concentration, matching the published data and indicating the appropriateness of that model. We suggest that Factor C is activated by multiple molecular interactions of Factor C with LPS aggregates on which it dimerises and that this explains why larger aggregates are less effective at activating Factor C than smaller ones.
KeywordsEndotoxin Lipopolysaccharide Factor C Statistical model Limulus amebocyte lysate
Number of LPS molecules on one side of a cubic aggregate
Number of LPS molecules in a cubic aggregate
Number of LPS molecules on one side of a square corresponding to the molecules present on the surface of a cubic aggregate
Number of LPS molecules in a square
Number of Factor C molecules
Fraction of activated Factor C in monomeric activation
Fraction of activated Factor C in dimeric activation
This study was supported by Grant-in-Aid for JSPS Fellows (Y.M.), JSPS KAKENHI Grant Number JP18J01966.
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