Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations

Human hemoglobin (Hb) is a benchmark protein of structural biology that shaped our view of allosterism over 60 years ago, with the introduction of the MWC model based on Perutz structures of the oxy(R) and deoxy(T) states and the more recent Tertiary Two-State model that proposed the existence of in...

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Authors: Bringas, Mauro, Petruk, Ariel Alcides, Estrin, Dario Ariel, Capece, Luciana, Marti, Marcelo Adrian
Format: article
Status:Published version
Publication Date:2017
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/65337
Online Access:http://hdl.handle.net/11336/65337
Access Level:Open access
Keyword:OXYGEN AFFINITY
HUMAN HEMOGLOBIN
QM/MM
MOLECULAR DYNAMICS
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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network_acronym_str AR
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repository_id_str
dc.title.none.fl_str_mv Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
title Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
spellingShingle Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
Bringas, Mauro
OXYGEN AFFINITY
HUMAN HEMOGLOBIN
QM/MM
MOLECULAR DYNAMICS
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
title_short Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
title_full Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
title_fullStr Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
title_full_unstemmed Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
title_sort Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
dc.creator.none.fl_str_mv Bringas, Mauro
Petruk, Ariel Alcides
Estrin, Dario Ariel
Capece, Luciana
Marti, Marcelo Adrian
author Bringas, Mauro
author_facet Bringas, Mauro
Petruk, Ariel Alcides
Estrin, Dario Ariel
Capece, Luciana
Marti, Marcelo Adrian
author_role author
author2 Petruk, Ariel Alcides
Estrin, Dario Ariel
Capece, Luciana
Marti, Marcelo Adrian
author2_role author
author
author
author
dc.subject.none.fl_str_mv OXYGEN AFFINITY
HUMAN HEMOGLOBIN
QM/MM
MOLECULAR DYNAMICS
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
topic OXYGEN AFFINITY
HUMAN HEMOGLOBIN
QM/MM
MOLECULAR DYNAMICS
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
description Human hemoglobin (Hb) is a benchmark protein of structural biology that shaped our view of allosterism over 60 years ago, with the introduction of the MWC model based on Perutz structures of the oxy(R) and deoxy(T) states and the more recent Tertiary Two-State model that proposed the existence of individual subunit states -"r" and "t"-, whose structure is yet unknown. Cooperative oxygen binding is essential for Hb function, and despite decades of research there are still open questions related to how tertiary and quaternary changes regulate oxygen affinity. In the present work, we have determined the free energy profiles of oxygen migration and for HisE7 gate opening, with QM/MM calculations of the oxygen binding energy in order to address the influence of tertiary differences in the control of oxygen affinity. Our results show that in the α subunit the low to high affinity transition is achieved by a proximal effect that mostly affects oxygen dissociation and is the driving force of the allosteric transition, while in the β subunit the affinity change results from a complex interplay of proximal and distal effects, including an increase in the HE7 gate opening, that as shown by free energy profiles promotes oxygen uptake.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/65337
Bringas, Mauro; Petruk, Ariel Alcides; Estrin, Dario Ariel; Capece, Luciana; Marti, Marcelo Adrian; Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations; Nature Publishing Group; Scientific Reports; 7; 1; 12-2017
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/65337
identifier_str_mv Bringas, Mauro; Petruk, Ariel Alcides; Estrin, Dario Ariel; Capece, Luciana; Marti, Marcelo Adrian; Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations; Nature Publishing Group; Scientific Reports; 7; 1; 12-2017
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-11259-0
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-11259-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1799196107723505664
spelling Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulationsBringas, MauroPetruk, Ariel AlcidesEstrin, Dario ArielCapece, LucianaMarti, Marcelo AdrianOXYGEN AFFINITYHUMAN HEMOGLOBINQM/MMMOLECULAR DYNAMICShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Human hemoglobin (Hb) is a benchmark protein of structural biology that shaped our view of allosterism over 60 years ago, with the introduction of the MWC model based on Perutz structures of the oxy(R) and deoxy(T) states and the more recent Tertiary Two-State model that proposed the existence of individual subunit states -"r" and "t"-, whose structure is yet unknown. Cooperative oxygen binding is essential for Hb function, and despite decades of research there are still open questions related to how tertiary and quaternary changes regulate oxygen affinity. In the present work, we have determined the free energy profiles of oxygen migration and for HisE7 gate opening, with QM/MM calculations of the oxygen binding energy in order to address the influence of tertiary differences in the control of oxygen affinity. Our results show that in the α subunit the low to high affinity transition is achieved by a proximal effect that mostly affects oxygen dissociation and is the driving force of the allosteric transition, while in the β subunit the affinity change results from a complex interplay of proximal and distal effects, including an increase in the HE7 gate opening, that as shown by free energy profiles promotes oxygen uptake.Fil: Bringas, Mauro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Petruk, Ariel Alcides. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaNature Publishing Group2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/65337Bringas, Mauro; Petruk, Ariel Alcides; Estrin, Dario Ariel; Capece, Luciana; Marti, Marcelo Adrian; Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations; Nature Publishing Group; Scientific Reports; 7; 1; 12-20172045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-017-11259-0info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-017-11259-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T14:15:01Zoai:ri.conicet.gov.ar:11336/65337instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982024-05-08 14:15:01.876CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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