title: Mutant hemoglobins (alpha 119-Ala and beta 55-Ser): functions related to high-altitude respiration in geese.
abstract: The unusually high blood-O2 affinity in the bar-headed and Andean geese is a necessary adaptation for migration across high mountain ranges. The amino acid residues alpha-119 and beta-55, which form an alpha 1 beta 1 contact in human hemoglobin (Hb), are altered in bar-headed and Andean geese, respectively, which suggests that loss of this contact increases O2 affinity. Two mutant human Hbs with equivalent mutations at these sites prepared by site-directed mutagenesis show the same increase in O2 affinity compared with Hb A, which indicates that these mutations are responsible for the changes in the protein. The intrinsic affinity difference compared with native Hb A is amplified by organic phosphates. Whereas the recombinant and native Hbs displayed similar sensitivities to pH, chloride, and 2,3-diphosphoglycerate, the oxygenation heat of the alpha-chain mutant decreased in the presence of 2,3-diphosphoglycerate. O2 association constants for the deoxygenated state of the alpha-mutant were about three times those for Hb A. The mutant Hb analogously exhibited higher affinity constants for binding the first three O2 molecules. Calculated heme-heme interaction energies indicated that loss of a single contact, resulting in destabilization of the deoxy (tense) structure, underlies the increased O2 affinity. Adaptations securing Hb-O2 binding at extreme altitude are discussed.
authors.affiliation: Department of Zoophysiology, Aarhus University, Denmark.
authors.forename: R E
authors.initials: RE
authors.lastname: Weber
authors.forename: T H
authors.initials: TH
authors.lastname: Jessen
authors.forename: H
authors.initials: H
authors.lastname: Malte
authors.forename: J
authors.initials: J
authors.lastname: Tame
mesh_terms: D019794:2,3-Diphosphoglycerate; D000328:Adult; D000531:Altitude; D000818:Animals; D004163:Diphosphoglyceric Acids / Q000494:pharmacology; D005777:Geese / Q000502:physiology*; D005784:Gene Amplification / Q000502:physiology; D006441:Hemoglobin A / Q000235:genetics / Q000378:metabolism; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010101:Oxygen Consumption / Q000502:physiology*; D013696:Temperature
chemical_list: D004163:Diphosphoglyceric Acids; D006455:Hemoglobins, Abnormal; D019794:2,3-Diphosphoglycerate; D006441:Hemoglobin A