Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure

Masayoshi Takayanagi; Ikuo Kurisaki; Masataka Nagaoka

doi:10.1038/srep04601

Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure

Masayoshi Takayanagi, Ikuo Kurisaki, Masataka Nagaoka^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O₂) act as a ''site-specific'' homotropic effector, or the successive O₂ binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O₂ allostery. Our simulation results revealed that the solution environment of high O₂ partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional ''non-site-specific'' allosteric effect of O₂. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view.

Original language	English
Article number	04601
Journal	Scientific reports
Volume	3
DOIs	https://doi.org/10.1038/srep04601
Publication status	Published - 2014 Apr 8
Externally published	Yes

ASJC Scopus subject areas

General

Access to Document

10.1038/srep04601

Cite this

@article{b5228bfd2c7d46aa9e19f3db8fe0d338,

title = "Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure",

abstract = "Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O2) act as a ''site-specific'' homotropic effector, or the successive O2 binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O2 allostery. Our simulation results revealed that the solution environment of high O2 partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional ''non-site-specific'' allosteric effect of O2. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view.",

author = "Masayoshi Takayanagi and Ikuo Kurisaki and Masataka Nagaoka",

note = "Funding Information: This work was partially supported by a Grant-in-Aid for the 21st Century COE program {\textquoteleft}{\textquoteleft}Frontiers of Computational Science{\textquoteright}{\textquoteright} at Nagoya University and also by a Grant-in-Aid for Science Research from the Ministry of Education, Culture, Sport, Science and Technology in Japan and the Core Research for Evolutional Science and Technology (CREST) {\textquoteleft}{\textquoteleft}Creation of Innovative Functional Materials with Advanced Properties by Hyper-nano-space Design{\textquoteright}{\textquoteright} and {\textquoteleft}{\textquoteleft}Establishment of Molecular Technology towards the Creation of New Functions{\textquoteright}{\textquoteright} from the Japan Science and Technology Agency. I.K., also thanks for the support from Japan Society for the Promotion of Science (JSPS) by the Research Fellowship for Young Scientist.",

year = "2014",

month = apr,

day = "8",

doi = "10.1038/srep04601",

language = "English",

volume = "3",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure

AU - Takayanagi, Masayoshi

AU - Kurisaki, Ikuo

AU - Nagaoka, Masataka

N1 - Funding Information: This work was partially supported by a Grant-in-Aid for the 21st Century COE program ‘‘Frontiers of Computational Science’’ at Nagoya University and also by a Grant-in-Aid for Science Research from the Ministry of Education, Culture, Sport, Science and Technology in Japan and the Core Research for Evolutional Science and Technology (CREST) ‘‘Creation of Innovative Functional Materials with Advanced Properties by Hyper-nano-space Design’’ and ‘‘Establishment of Molecular Technology towards the Creation of New Functions’’ from the Japan Science and Technology Agency. I.K., also thanks for the support from Japan Society for the Promotion of Science (JSPS) by the Research Fellowship for Young Scientist.

PY - 2014/4/8

Y1 - 2014/4/8

N2 - Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O2) act as a ''site-specific'' homotropic effector, or the successive O2 binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O2 allostery. Our simulation results revealed that the solution environment of high O2 partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional ''non-site-specific'' allosteric effect of O2. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view.

AB - Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O2) act as a ''site-specific'' homotropic effector, or the successive O2 binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O2 allostery. Our simulation results revealed that the solution environment of high O2 partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional ''non-site-specific'' allosteric effect of O2. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view.

UR - http://www.scopus.com/inward/record.url?scp=84910119234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84910119234&partnerID=8YFLogxK

U2 - 10.1038/srep04601

DO - 10.1038/srep04601

M3 - Article

C2 - 24710521

AN - SCOPUS:84910119234

SN - 2045-2322

VL - 3

JO - Scientific reports

JF - Scientific reports

M1 - 04601

ER -

Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this