Oxygenation properties and underlying molecular mechanisms of hemoglobins in plateau zokor ().

The plateau zokor () is a species of subterranean rodent endemic to the Tibetan Plateau. It is well adapted to the cold and hypoxic and hypercapnic burrow. To study the oxygenation properties of plateau zokor hemoglobins (Hbs), we measured intrinsic Hb-O affinities and their sensitivities to pH (Bohr effect); CO; Cl, 2,3-diphosphoglycerate (DPG); and temperature using purified Hbs from zokor and mouse. The optimal deoxyHb model of plateau zokor was constructed and used to study its structural characteristics by molecular dynamics simulations. O binding results revealed that plateau zokor Hbs exhibit remarkably high intrinsic Hb-O affinity, low CO effects compared with human and the relatively low anion allosteric effector sensitivities (DPG and Cl) at normal temperature, which would safeguard the pulmonary Hb-O loading under hypoxic and hypercapnic conditions. Furthermore, the high anion allosteric effector sensitivities at low temperature and low temperature sensitivities of plateau zokor Hbs would facilitate the releasing of O in cold extremities and metabolic tissues. However, the high Hb-O affinity of plateau zokor is not compensated by high pH sensitivity as the Bohr factors of plateau zokor Hbs were as low as those of mouse. The results of molecular dynamics simulations revealed the reduced hydrogen bonding between the α1β1- and α2β2-dimer interface of deoxyHb in zokor compared with mouse. It may be the primary mechanism of the high intrinsic Hb-O affinities in zokor. Specifically, substitution of the 131Ser→Asn in the α2-chain weakened the connection between α1- and β2-subunit.