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Title: Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

Abstract

Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant. Highland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric hemoglobin molecules. The analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE; National Institutes of Health (NIH)
OSTI Identifier:
1349928
Resource Type:
Journal Article
Resource Relation:
Journal Name: PLoS ONE; Journal Volume: 12; Journal Issue: 3
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Inoguchi, Noriko, Mizuno, Nobuhiro, Baba, Seiki, Kumasaka, Takashi, Natarajan, Chandrasekhar, Storz, Jay F., Moriyama, Hideaki, and Permyakov, Eugene A. Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice. United States: N. p., 2017. Web. doi:10.1371/journal.pone.0174921.
Inoguchi, Noriko, Mizuno, Nobuhiro, Baba, Seiki, Kumasaka, Takashi, Natarajan, Chandrasekhar, Storz, Jay F., Moriyama, Hideaki, & Permyakov, Eugene A. Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice. United States. doi:10.1371/journal.pone.0174921.
Inoguchi, Noriko, Mizuno, Nobuhiro, Baba, Seiki, Kumasaka, Takashi, Natarajan, Chandrasekhar, Storz, Jay F., Moriyama, Hideaki, and Permyakov, Eugene A. Fri . "Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice". United States. doi:10.1371/journal.pone.0174921.
@article{osti_1349928,
title = {Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice},
author = {Inoguchi, Noriko and Mizuno, Nobuhiro and Baba, Seiki and Kumasaka, Takashi and Natarajan, Chandrasekhar and Storz, Jay F. and Moriyama, Hideaki and Permyakov, Eugene A.},
abstractNote = {Deer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant. Highland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric hemoglobin molecules. The analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.},
doi = {10.1371/journal.pone.0174921},
journal = {PLoS ONE},
number = 3,
volume = 12,
place = {United States},
year = {Fri Mar 31 00:00:00 EDT 2017},
month = {Fri Mar 31 00:00:00 EDT 2017}
}