title: Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding.
abstract: This report establishes a correlation between two known properties of the human embryonic hemoglobins-- their weak subunit assemblies as demonstrated here by gel filtration at very dilute protein concentrations and their high oxygen affinities and reduced cooperativities reported previously by others but without a mechanistic basis. We demonstrate here that their high oxygen affinities are a consequence of their weak assemblies. Weak vs strong hemoglobin tetramers represent a regulatory mechanism to modulate oxygen binding capacity by altering the equilibrium between the various steps in the assembly process that can be described as an inverse allosteric effect.
authors.affiliation: Department of Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: Lois R
authors.initials: LR
authors.lastname: Manning
authors.affiliation: Information Technology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Popowicz
authors.affiliation: Laboratory for Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Padovan
authors.affiliation: Laboratory for Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.affiliation: Department of Biology, Northeastern University, Boston, MA 02115, USA. Electronic address: j.manning@neu.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Manning
mesh_terms: D000494:Allosteric Regulation; D002850:Chromatography, Gel / Q000379:methods*; D004622:Embryo, Mammalian / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D010100:Oxygen
keywords: Development; Gel filtration; Hemoglobin; Oxygen affinity; Subunit assembly