Alteration of the α1 β22 β1 subunit interface contributes to the increased hemoglobinoxygen affinity of high-altitude deer mice

Noriko Inoguchi, Nobuhiro Mizuno, Seiki Baba, Takashi Kumasaka, Chandrasekhar Natarajan, Jay F Storz, Hideaki Moriyama

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 α1 β22 β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.

Original languageEnglish (US)
Article numbere0174921
JournalPLoS One
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2017

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Peromyscus
hemoglobin
Hemoglobins
lowlands
highlands
crystal structure
Oxygen
mutation
oxygen
Mutation
Crystals
Peromyscus maniculatus
Rocky Mountain region
heme
Heme
crystals
Crystal structure
Molecules

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Alteration of the α1 β22 β1 subunit interface contributes to the increased hemoglobinoxygen affinity of high-altitude deer mice. / Inoguchi, Noriko; Mizuno, Nobuhiro; Baba, Seiki; Kumasaka, Takashi; Natarajan, Chandrasekhar; Storz, Jay F; Moriyama, Hideaki.

In: PLoS One, Vol. 12, No. 3, e0174921, 01.03.2017.

Research output: Contribution to journalArticle

Inoguchi, Noriko ; Mizuno, Nobuhiro ; Baba, Seiki ; Kumasaka, Takashi ; Natarajan, Chandrasekhar ; Storz, Jay F ; Moriyama, Hideaki. / Alteration of the α1 β22 β1 subunit interface contributes to the increased hemoglobinoxygen affinity of high-altitude deer mice. In: PLoS One. 2017 ; Vol. 12, No. 3.
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abstract = "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 {\AA}. Using the smaller unit cell crystal, the structure was solved at 2.2 {\AA} 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 α1 β2 /α2 β1 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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AU - Kumasaka, Takashi

AU - Natarajan, Chandrasekhar

AU - Storz, Jay F

AU - Moriyama, Hideaki

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N2 - 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 α1 β2 /α2 β1 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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