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Abstract:

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. © 2017 The Author(s).

Registro:

Documento: Artículo
Título:Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations
Autor:Bringas, M.; Petruk, A.A.; Estrin, D.A.; Capece, L.; Martí, M.A.
Filiación:Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1428EHA, Argentina
Instituto de Química Física de Los Materiales, Medio Ambiente y Energía, CONICET, Ciudad de Buenos Aires, C1428EHA, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, C1428EHA, Argentina
Instituto de Química Biológica, Facultad de Ciencias Exactas y Naturales, CONICET, Ciudad de Buenos Aires, C1428EHA, Argentina
Año:2017
Volumen:7
Número:1
DOI: http://dx.doi.org/10.1038/s41598-017-11259-0
Título revista:Scientific Reports
Título revista abreviado:Sci. Rep.
ISSN:20452322
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v7_n1_p_Bringas

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Citas:

---------- APA ----------
Bringas, M., Petruk, A.A., Estrin, D.A., Capece, L. & Martí, M.A. (2017) . Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations. Scientific Reports, 7(1).
http://dx.doi.org/10.1038/s41598-017-11259-0
---------- CHICAGO ----------
Bringas, M., Petruk, A.A., Estrin, D.A., Capece, L., Martí, M.A. "Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations" . Scientific Reports 7, no. 1 (2017).
http://dx.doi.org/10.1038/s41598-017-11259-0
---------- MLA ----------
Bringas, M., Petruk, A.A., Estrin, D.A., Capece, L., Martí, M.A. "Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations" . Scientific Reports, vol. 7, no. 1, 2017.
http://dx.doi.org/10.1038/s41598-017-11259-0
---------- VANCOUVER ----------
Bringas, M., Petruk, A.A., Estrin, D.A., Capece, L., Martí, M.A. Tertiary and quaternary structural basis of oxygen affinity in human hemoglobin as revealed by multiscale simulations. Sci. Rep. 2017;7(1).
http://dx.doi.org/10.1038/s41598-017-11259-0