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Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

BACKGROUND: 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 hemoglob...

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Autores principales: Inoguchi, Noriko, Mizuno, Nobuhiro, Baba, Seiki, Kumasaka, Takashi, Natarajan, Chandrasekhar, Storz, Jay F., Moriyama, Hideaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376325/
https://www.ncbi.nlm.nih.gov/pubmed/28362841
http://dx.doi.org/10.1371/journal.pone.0174921
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author Inoguchi, Noriko
Mizuno, Nobuhiro
Baba, Seiki
Kumasaka, Takashi
Natarajan, Chandrasekhar
Storz, Jay F.
Moriyama, Hideaki
author_facet Inoguchi, Noriko
Mizuno, Nobuhiro
Baba, Seiki
Kumasaka, Takashi
Natarajan, Chandrasekhar
Storz, Jay F.
Moriyama, Hideaki
author_sort Inoguchi, Noriko
collection PubMed
description BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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 α(1)β(2)/α(2)β(1) intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.
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spelling pubmed-53763252017-04-07 Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice Inoguchi, Noriko Mizuno, Nobuhiro Baba, Seiki Kumasaka, Takashi Natarajan, Chandrasekhar Storz, Jay F. Moriyama, Hideaki PLoS One Research Article BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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 α(1)β(2)/α(2)β(1) intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites. Public Library of Science 2017-03-31 /pmc/articles/PMC5376325/ /pubmed/28362841 http://dx.doi.org/10.1371/journal.pone.0174921 Text en © 2017 Inoguchi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Inoguchi, Noriko
Mizuno, Nobuhiro
Baba, Seiki
Kumasaka, Takashi
Natarajan, Chandrasekhar
Storz, Jay F.
Moriyama, Hideaki
Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
title Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
title_full Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
title_fullStr Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
title_full_unstemmed Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
title_short Alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
title_sort alteration of the α(1)β(2)/α(2)β(1) subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376325/
https://www.ncbi.nlm.nih.gov/pubmed/28362841
http://dx.doi.org/10.1371/journal.pone.0174921
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