Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice
(A) Sequence alignment of deer mouse highland (H) and lowland (L) hemoglobin. The substitutions are highlighted in blue. The sequences were obtained from the deposited structures as follows: highland deer mouse hemoglobin (PDB ID: 5KER), lowland deer mouse hemoglobin (4H2L), human hemoglobin (2DN1). (B) Orientation of two tetrameric hemoglobin molecules in an asymmetric unit. The α subunits are colored in cyan, and the β subunits are colored in gray. Heme in each subunit is shown as a red stick model, and the active site without ligand assignment is indicated with a black circle. (C) Structural difference in main chain folding with an emphasis on αHis45 coordinates. Tetrameric highland hemoglobin (5KER; cyan) and lowland hemoglobin (4H2L, pink) are superimposed by PyMOL. The residues around the active site and the nearby loop region are shown in the cartoon model. Key residues and helices containing these residues in the α subunit (chain A) are shown in the stick model and the cartoon model.