The high blood-O2 affinity of the bar-headed goose (Anser indicus) is an integral component of the biochemical and physiological adaptations that allow this hypoxia-tolerant species to undertake migratory flights over the Himalayas. The high blood-O2 affinity of this species was originally attributed to a single amino acid substitution of the major hemoglobin (Hb) isoform, HbA, which was thought to destabilize the low-affinity T-state, thereby shifting the T-R allosteric equilibrium towards the high-affinity R-state. Surprisingly, this mechanistic hypothesis has never been addressed using native proteins purified from blood. Here, we report a detailed analysis of O2 equilibria and kinetics of native major HbA and minor HbD isoforms from bar-headed goose and greylag goose (Anser anser), a strictly lowland species, to identify and characterize the mechanistic basis for the adaptive change in Hb function. We find that HbA and HbD of bar-headed goose have consistently higher O2 affinities than those of the greylag goose. The corresponding Hb isoforms of the two species are equally responsive to physiological allosteric cofactors and have similar Bohr effects. Thermodynamic analyses of O2 equilibrium curves according to the two-state MWC model revealed higher R-state O2 affinities in the bar-headed goose Hbs, associated with lower O2 dissociation rates, compared to the greylag goose. Conversely, the T-state was not destabilized and the T-R allosteric equilibrium was unaltered in bar-headed goose Hbs. The physiological implication of these results is that increased R-state affinity allows for enhanced O2 saturation in the lungs during hypoxia, but without impairing O2 delivery to tissues.
Allosteric mechanisms underlying the adaptive increase in hemoglobin-oxygen affinity of the bar-headed goose
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Agnieszka Jendroszek, Hans Malte, Cathrine B. Overgaard, Kristian Beedholm, Chandrasekhar Natarajan, Roy E. Weber, Jay F. Storz, Angela Fago; Allosteric mechanisms underlying the adaptive increase in hemoglobin-oxygen affinity of the bar-headed goose. J Exp Biol 2018; jeb.185470. doi: https://doi.org/10.1242/jeb.185470
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