Using the MWC model to describe heterotropic interactions in hemoglobin.
Hemoglobin is a classical model allosteric protein. Research on hemoglobin parallels the development of key cooperativity and allostery concepts, such as the 'all-or-none' Hill formalism, the stepwise Adair binding formulation and the concerted Monod-Wymann-Changuex (MWC) allosteric model....
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182871&type=printable |
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| author | Olga Rapp Ofer Yifrach |
| author_facet | Olga Rapp Ofer Yifrach |
| author_sort | Olga Rapp |
| collection | DOAJ |
| description | Hemoglobin is a classical model allosteric protein. Research on hemoglobin parallels the development of key cooperativity and allostery concepts, such as the 'all-or-none' Hill formalism, the stepwise Adair binding formulation and the concerted Monod-Wymann-Changuex (MWC) allosteric model. While it is clear that the MWC model adequately describes the cooperative binding of oxygen to hemoglobin, rationalizing the effects of H+, CO2 or organophosphate ligands on hemoglobin-oxygen saturation using the same model remains controversial. According to the MWC model, allosteric ligands exert their effect on protein function by modulating the quaternary conformational transition of the protein. However, data fitting analysis of hemoglobin oxygen saturation curves in the presence or absence of inhibitory ligands persistently revealed effects on both relative oxygen affinity (c) and conformational changes (L), elementary MWC parameters. The recent realization that data fitting analysis using the traditional MWC model equation may not provide reliable estimates for L and c thus calls for a re-examination of previous data using alternative fitting strategies. In the current manuscript, we present two simple strategies for obtaining reliable estimates for MWC mechanistic parameters of hemoglobin steady-state saturation curves in cases of both evolutionary and physiological variations. Our results suggest that the simple MWC model provides a reasonable description that can also account for heterotropic interactions in hemoglobin. The results, moreover, offer a general roadmap for successful data fitting analysis using the MWC model. |
| format | Article |
| id | doaj-art-12bc4f7ebb7749be89fb65b8be3e7433 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-12bc4f7ebb7749be89fb65b8be3e74332025-08-20T02:46:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01128e018287110.1371/journal.pone.0182871Using the MWC model to describe heterotropic interactions in hemoglobin.Olga RappOfer YifrachHemoglobin is a classical model allosteric protein. Research on hemoglobin parallels the development of key cooperativity and allostery concepts, such as the 'all-or-none' Hill formalism, the stepwise Adair binding formulation and the concerted Monod-Wymann-Changuex (MWC) allosteric model. While it is clear that the MWC model adequately describes the cooperative binding of oxygen to hemoglobin, rationalizing the effects of H+, CO2 or organophosphate ligands on hemoglobin-oxygen saturation using the same model remains controversial. According to the MWC model, allosteric ligands exert their effect on protein function by modulating the quaternary conformational transition of the protein. However, data fitting analysis of hemoglobin oxygen saturation curves in the presence or absence of inhibitory ligands persistently revealed effects on both relative oxygen affinity (c) and conformational changes (L), elementary MWC parameters. The recent realization that data fitting analysis using the traditional MWC model equation may not provide reliable estimates for L and c thus calls for a re-examination of previous data using alternative fitting strategies. In the current manuscript, we present two simple strategies for obtaining reliable estimates for MWC mechanistic parameters of hemoglobin steady-state saturation curves in cases of both evolutionary and physiological variations. Our results suggest that the simple MWC model provides a reasonable description that can also account for heterotropic interactions in hemoglobin. The results, moreover, offer a general roadmap for successful data fitting analysis using the MWC model.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182871&type=printable |
| spellingShingle | Olga Rapp Ofer Yifrach Using the MWC model to describe heterotropic interactions in hemoglobin. PLoS ONE |
| title | Using the MWC model to describe heterotropic interactions in hemoglobin. |
| title_full | Using the MWC model to describe heterotropic interactions in hemoglobin. |
| title_fullStr | Using the MWC model to describe heterotropic interactions in hemoglobin. |
| title_full_unstemmed | Using the MWC model to describe heterotropic interactions in hemoglobin. |
| title_short | Using the MWC model to describe heterotropic interactions in hemoglobin. |
| title_sort | using the mwc model to describe heterotropic interactions in hemoglobin |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0182871&type=printable |
| work_keys_str_mv | AT olgarapp usingthemwcmodeltodescribeheterotropicinteractionsinhemoglobin AT oferyifrach usingthemwcmodeltodescribeheterotropicinteractionsinhemoglobin |