6533b853fe1ef96bd12ac2c6
RESEARCH PRODUCT
Structure of the altitude adapted hemoglobin of Guinea pig in the R2-state
Elmar JaenickeBruno Pairetsubject
Models MolecularSteric effectsGuinea PigsBiophysicslcsh:Medicinechemistry.chemical_elementCrystallography X-RayBiochemistryOxygen570 Life sciencesGuinea pigHemoglobinsAltitudeBiophysics/Macromolecular Assemblies and MachinesAnimalsProlineProtein Structure Quaternarylcsh:ScienceHistidineMultidisciplinaryProtein StabilityAltitudelcsh:ROxygen transportAdaptation PhysiologicalBiochemistry/Molecular EvolutionBiochemistry/Macromolecular Assemblies and MachinesBiochemistrychemistryBiophysicsPhysiology/Respiratory Physiologylcsh:QHemoglobinResearch Article570 Biowissenschaftendescription
Background: Guinea pigs are considered to be genetically adapted to a high altitude environment based on the consistent finding of a high oxygen affinity of their blood. Methodology/Principal Findings: The crystal structure of guinea pig hemoglobin at 1.8 A u resolution suggests that the increased oxygen affinity of guinea pig hemoglobin can be explained by two factors, namely a decreased stability of the Tstate and an increased stability of the R2-state. The destabilization of the T-state can be related to the substitution of a highly conserved proline (P44) to histidine (H44) in the a-subunit, which causes a steric hindrance with H97 of the b-subunit in the switch region. The stabilization of the R2-state is caused by two additional salt bridges at the b1/b2 interface. Conclusions/Significance: Both factors together are supposed to serve to shift the equilibrium between the conformational states towards the high affinity relaxed states resulting in an increased oxygen affinity.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-08-01 |