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Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin

[Image: see text] Allosteric regulation is an essential function of many proteins that control a variety of different processes such as catalysis, signal transduction, and gene regulation. Structural rearrangements have historically been considered the main means of communication between different p...

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Autores principales: Laine, Jennifer M., Amat, Miguel, Morgan, Brittany R., Royer, William E., Massi, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245988/
https://www.ncbi.nlm.nih.gov/pubmed/25356908
http://dx.doi.org/10.1021/bi500591s
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author Laine, Jennifer M.
Amat, Miguel
Morgan, Brittany R.
Royer, William E.
Massi, Francesca
author_facet Laine, Jennifer M.
Amat, Miguel
Morgan, Brittany R.
Royer, William E.
Massi, Francesca
author_sort Laine, Jennifer M.
collection PubMed
description [Image: see text] Allosteric regulation is an essential function of many proteins that control a variety of different processes such as catalysis, signal transduction, and gene regulation. Structural rearrangements have historically been considered the main means of communication between different parts of a protein. Recent studies have highlighted the importance, however, of changes in protein flexibility as an effective way to mediate allosteric communication across a protein. Scapharca dimeric hemoglobin (HbI) is the simplest possible allosteric system, with cooperative ligand binding between two identical subunits. Thermodynamic equilibrium studies of the binding of oxygen to HbI have shown that cooperativity is an entropically driven effect. The change in entropy of the system observed upon ligand binding may arise from changes in the protein, the ligand, or the water of the system. The goal of this study is to determine the contribution of the change in entropy of the protein backbone to HbI cooperative binding. Molecular dynamics simulations and nuclear magnetic resonance relaxation techniques have revealed that the fast internal motions of HbI contribute to the cooperative binding to carbon monoxide in two ways: (1) by contributing favorably to the free energy of the system and (2) by participating in the cooperative mechanism at the HbI subunit interface. The internal dynamics of the weakly cooperative HbI mutant, F97Y, were also investigated with the same methods. The changes in backbone NH dynamics observed for F97Y HbI upon ligand binding are not as large as for the wild type, in agreement with the reduced cooperativity observed for this mutant. The results of this study indicate that interface flexibility and backbone conformational entropy of HbI participate in and are important for the cooperative mechanism of carbon monoxide binding.
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spelling pubmed-42459882015-10-30 Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin Laine, Jennifer M. Amat, Miguel Morgan, Brittany R. Royer, William E. Massi, Francesca Biochemistry [Image: see text] Allosteric regulation is an essential function of many proteins that control a variety of different processes such as catalysis, signal transduction, and gene regulation. Structural rearrangements have historically been considered the main means of communication between different parts of a protein. Recent studies have highlighted the importance, however, of changes in protein flexibility as an effective way to mediate allosteric communication across a protein. Scapharca dimeric hemoglobin (HbI) is the simplest possible allosteric system, with cooperative ligand binding between two identical subunits. Thermodynamic equilibrium studies of the binding of oxygen to HbI have shown that cooperativity is an entropically driven effect. The change in entropy of the system observed upon ligand binding may arise from changes in the protein, the ligand, or the water of the system. The goal of this study is to determine the contribution of the change in entropy of the protein backbone to HbI cooperative binding. Molecular dynamics simulations and nuclear magnetic resonance relaxation techniques have revealed that the fast internal motions of HbI contribute to the cooperative binding to carbon monoxide in two ways: (1) by contributing favorably to the free energy of the system and (2) by participating in the cooperative mechanism at the HbI subunit interface. The internal dynamics of the weakly cooperative HbI mutant, F97Y, were also investigated with the same methods. The changes in backbone NH dynamics observed for F97Y HbI upon ligand binding are not as large as for the wild type, in agreement with the reduced cooperativity observed for this mutant. The results of this study indicate that interface flexibility and backbone conformational entropy of HbI participate in and are important for the cooperative mechanism of carbon monoxide binding. American Chemical Society 2014-10-30 2014-11-25 /pmc/articles/PMC4245988/ /pubmed/25356908 http://dx.doi.org/10.1021/bi500591s Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Laine, Jennifer M.
Amat, Miguel
Morgan, Brittany R.
Royer, William E.
Massi, Francesca
Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin
title Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin
title_full Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin
title_fullStr Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin
title_full_unstemmed Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin
title_short Insight into the Allosteric Mechanism of Scapharca Dimeric Hemoglobin
title_sort insight into the allosteric mechanism of scapharca dimeric hemoglobin
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245988/
https://www.ncbi.nlm.nih.gov/pubmed/25356908
http://dx.doi.org/10.1021/bi500591s
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