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

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...

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Autores principales: Jagusiak, A., Konieczny, L., Król, M., Marszałek, P., Piekarska, B., Piwowar, P., Roterman, I., Rybarska, J., Stopa, B., Zemanek, G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440395/
https://www.ncbi.nlm.nih.gov/pubmed/25429660
http://dx.doi.org/10.2174/1389557514666141127150803
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author Jagusiak, A.
Konieczny, L.
Król, M.
Marszałek, P.
Piekarska, B.
Piwowar, P.
Roterman, I.
Rybarska, J.
Stopa, B.
Zemanek, G.
author_facet Jagusiak, A.
Konieczny, L.
Król, M.
Marszałek, P.
Piekarska, B.
Piwowar, P.
Roterman, I.
Rybarska, J.
Stopa, B.
Zemanek, G.
author_sort Jagusiak, A.
collection PubMed
description 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.
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spelling pubmed-44403952015-05-22 Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool Jagusiak, A. Konieczny, L. Król, M. Marszałek, P. Piekarska, B. Piwowar, P. Roterman, I. Rybarska, J. Stopa, B. Zemanek, G. Mini Rev Med Chem Article 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. Bentham Science Publishers 2014-11 2014-11 /pmc/articles/PMC4440395/ /pubmed/25429660 http://dx.doi.org/10.2174/1389557514666141127150803 Text en © 2014 Bentham Science Publishers http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Jagusiak, A.
Konieczny, L.
Król, M.
Marszałek, P.
Piekarska, B.
Piwowar, P.
Roterman, I.
Rybarska, J.
Stopa, B.
Zemanek, G.
Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool
title Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool
title_full Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool
title_fullStr Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool
title_full_unstemmed Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool
title_short Intramolecular Immunological Signal Hypothesis Revived - Structural Background of Signalling Revealed by Using Congo Red as a Specific Tool
title_sort intramolecular immunological signal hypothesis revived - structural background of signalling revealed by using congo red as a specific tool
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440395/
https://www.ncbi.nlm.nih.gov/pubmed/25429660
http://dx.doi.org/10.2174/1389557514666141127150803
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