title: Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice.
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 α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America.
authors.forename: Noriko
authors.initials: N
authors.lastname: Inoguchi
authors.affiliation: Protein Crystal Analysis Division, Japan Synchrotron Radiation Research Institute, Sayo, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Protein Crystal Analysis Division, Japan Synchrotron Radiation Research Institute, Sayo, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Baba
authors.affiliation: Protein Crystal Analysis Division, Japan Synchrotron Radiation Research Institute, Sayo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumasaka
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Natarajan
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Storz
authors.affiliation: School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America.
authors.forename: Hideaki
authors.identifier: http://orcid.org/0000-0001-7815-1181
authors.initials: H
authors.lastname: Moriyama
mesh_terms: D000531:Altitude; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D010542:Peromyscus / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D014961:X-Ray Diffraction
chemical_list: D006454:Hemoglobins; D010100:Oxygen