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Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool

Author(s): A. Jagusiak, L. Konieczny, M. Krol, P. Marszalek, B. Piekarska, P. Piwowar, I. Roterman, J. Rybarska, B. Stopa and G. Zemanek

Volume 14, Issue 13, 2014

Page: [1104 - 1113] Pages: 10

DOI: 10.2174/1389557514666141127150803

open access plus

Abstract

Micellar structures formed by self-assembling Congo red molecules bind to proteins penetrating into functionrelated unstable packing areas. Here, we have used Congo red - a supramolecular protein ligand to investigate how the intramolecular structural changes that take place in antibodies following antigen binding lead to complement activation. According to our findings, Congo red binding significantly enhances the formation of antigen-antibody complexes. As a result, even low-affinity transiently binding antibodies can participate in immune complexes in the presence of Congo red, although immune complexes formed by these antibodies fail to trigger the complement cascade. This indicates that binding of antibodies to the antigen may not, by itself, fulfill the necessary conditions to generate the signal which triggers effector activity. These findings, together with the results of molecular dynamics simulation studies, enable us to conclude that, apart from the necessary assembling of antibodies, intramolecular structural changes generated by strains which associate high- affinity bivalent antibody fitting to antigen determinants are also required to cross the complement activation threshold.

Keywords: C1q binding, complement activation, Congo red, immune complexation, supramolecular protein ligand.

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