Allosteric mechanisms underlying the adaptive increase in hemoglobin-oxygen affinity of the bar-headed goose

TY - JOUR

T1 - Allosteric mechanisms underlying the adaptive increase in hemoglobin-oxygen affinity of the bar-headed goose

AU - Jendroszek, Agnieszka

AU - Malte, Hans

AU - Overgaard, Cathrine B

AU - Beedholm, Kristian

AU - Natarajan, Chandrasekhar

AU - Weber, Roy E

AU - Storz, Jay F

AU - Fago, Angela

N1 - © 2018. Published by The Company of Biologists Ltd.

PY - 2018/9

Y1 - 2018/9

N2 - The high blood–O 2affinity 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–O 2affinity 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 O 2equilibria 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 O 2affinities 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 O 2equilibrium curves according to the two-state Monod–Wyman–Changeaux model revealed higher R-state O 2affinities in the bar-headed goose Hbs, associated with lower O 2dissociation rates, compared with 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 O 2saturation in the lungs during hypoxia, but without impairing O 2delivery to tissues.

AB - The high blood–O 2affinity 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–O 2affinity 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 O 2equilibria 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 O 2affinities 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 O 2equilibrium curves according to the two-state Monod–Wyman–Changeaux model revealed higher R-state O 2affinities in the bar-headed goose Hbs, associated with lower O 2dissociation rates, compared with 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 O 2saturation in the lungs during hypoxia, but without impairing O 2delivery to tissues.

KW - Adaptation

KW - Allostery

KW - Blood

KW - High-altitude

KW - Hypoxia

KW - Oxygen transport

UR - http://www.scopus.com/inward/record.url?scp=85054152506&partnerID=8YFLogxK

U2 - 10.1242/jeb.185470

DO - 10.1242/jeb.185470

M3 - Journal article

C2 - 30026237

SN - 0022-0949

VL - 221

JO - Journal of Experimental Biology

JF - Journal of Experimental Biology

IS - 18

M1 - 185470

ER -