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Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies

BACKGROUND: How antibodies recognize and bind to antigens can not be totally explained by rigid shape and electrostatic complimentarity models. Alternatively, pre-existing equilibrium hypothesis states that the native state of an antibody is not defined by a single rigid conformation but instead wit...

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Autor principal: Keskin, Ozlem
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1888692/
https://www.ncbi.nlm.nih.gov/pubmed/17509130
http://dx.doi.org/10.1186/1472-6807-7-31
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author Keskin, Ozlem
author_facet Keskin, Ozlem
author_sort Keskin, Ozlem
collection PubMed
description BACKGROUND: How antibodies recognize and bind to antigens can not be totally explained by rigid shape and electrostatic complimentarity models. Alternatively, pre-existing equilibrium hypothesis states that the native state of an antibody is not defined by a single rigid conformation but instead with an ensemble of similar conformations that co-exist at equilibrium. Antigens bind to one of the preferred conformations making this conformation more abundant shifting the equilibrium. RESULTS: Here, two antibodies, a germline antibody of 36–65 Fab and a monoclonal antibody, SPE7 are studied in detail to elucidate the mechanism of antibody-antigen recognition and to understand how a single antibody recognizes different antigens. An elastic network model, Anisotropic Network Model (ANM) is used in the calculations. Pre-existing equilibrium is not restricted to apply to antibodies. Intrinsic fluctuations of eight proteins, from different classes of proteins, such as enzymes, binding and transport proteins are investigated to test the suitability of the method. The intrinsic fluctuations are compared with the experimentally observed ligand induced conformational changes of these proteins. The results show that the intrinsic fluctuations obtained by theoretical methods correlate with structural changes observed when a ligand is bound to the protein. The decomposition of the total fluctuations serves to identify the different individual modes of motion, ranging from the most cooperative ones involving the overall structure, to the most localized ones. CONCLUSION: Results suggest that the pre-equilibrium concept holds for antibodies and the promiscuity of antibodies can also be explained this hypothesis: a limited number of conformational states driven by intrinsic motions of an antibody might be adequate to bind to different antigens.
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spelling pubmed-18886922007-06-06 Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies Keskin, Ozlem BMC Struct Biol Research Article BACKGROUND: How antibodies recognize and bind to antigens can not be totally explained by rigid shape and electrostatic complimentarity models. Alternatively, pre-existing equilibrium hypothesis states that the native state of an antibody is not defined by a single rigid conformation but instead with an ensemble of similar conformations that co-exist at equilibrium. Antigens bind to one of the preferred conformations making this conformation more abundant shifting the equilibrium. RESULTS: Here, two antibodies, a germline antibody of 36–65 Fab and a monoclonal antibody, SPE7 are studied in detail to elucidate the mechanism of antibody-antigen recognition and to understand how a single antibody recognizes different antigens. An elastic network model, Anisotropic Network Model (ANM) is used in the calculations. Pre-existing equilibrium is not restricted to apply to antibodies. Intrinsic fluctuations of eight proteins, from different classes of proteins, such as enzymes, binding and transport proteins are investigated to test the suitability of the method. The intrinsic fluctuations are compared with the experimentally observed ligand induced conformational changes of these proteins. The results show that the intrinsic fluctuations obtained by theoretical methods correlate with structural changes observed when a ligand is bound to the protein. The decomposition of the total fluctuations serves to identify the different individual modes of motion, ranging from the most cooperative ones involving the overall structure, to the most localized ones. CONCLUSION: Results suggest that the pre-equilibrium concept holds for antibodies and the promiscuity of antibodies can also be explained this hypothesis: a limited number of conformational states driven by intrinsic motions of an antibody might be adequate to bind to different antigens. BioMed Central 2007-05-17 /pmc/articles/PMC1888692/ /pubmed/17509130 http://dx.doi.org/10.1186/1472-6807-7-31 Text en Copyright © 2007 Keskin; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Keskin, Ozlem
Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies
title Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies
title_full Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies
title_fullStr Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies
title_full_unstemmed Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies
title_short Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies
title_sort binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1888692/
https://www.ncbi.nlm.nih.gov/pubmed/17509130
http://dx.doi.org/10.1186/1472-6807-7-31
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