Structure of the altitude adapted hemoglobin of guinea pig in the R2-state.
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.


RESULTS
The crystal structure of guinea pig hemoglobin at 1.8 A resolution suggests that the increased oxygen affinity of guinea pig hemoglobin can be explained by two factors, namely a decreased stability of the T-state 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 alpha-subunit, which causes a steric hindrance with H97 of the beta-subunit in the switch region. The stabilization of the R2-state is caused by two additional salt bridges at the beta1/beta2 interface.


CONCLUSIONS
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.
Pairet
Bruno
B
Institut für Molekulare Biophysik, Johannes Gutenberg Universität, Mainz, Germany.
Jaenicke
Elmar
E
D000222:Adaptation, Physiological; D000531:Altitude; D000818:Animals; D018360:Crystallography, X-Ray; D006168:Guinea Pigs / Q000502:physiology*; D006454:Hemoglobins / Q000737:chemistry*; D008958:Models, Molecular; D055550:Protein Stability; D020836:Protein Structure, Quaternary
D006454:Hemoglobins
Science. 1971 Jun 4;172(3987):1049-50
5573955
Comp Biochem Physiol A Physiol. 1994 Nov;109(3):675-80
8529009
Pflugers Arch. 1978 Aug 25;376(1):7-13
568243
Pflugers Arch. 1980 Mar;384(2):109-15
7189874
Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7841-4
9223274
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
15572765
Hemoglobin. 1982;6(1):43-9
7068434
J Mol Biol. 1965 May;12:88-118
14343300
Respir Physiol Neurobiol. 2007 Sep 30;158(2-3):121-7
17449336
Evolution. 1988 Jul;42(4):689-697
28563873
Protein Pept Lett. 2009;16(4):444-6
19356144
Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6519-22
1862080
J Mol Biol. 1983 Nov 25;171(1):31-59
6644819
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
15299374
Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):517-20
12525687
Respir Physiol. 1969 Oct;7(3):278-86
5823837
Hoppe Seylers Z Physiol Chem. 1979 Dec;360(12):1941-6
527943
Biol Chem Hoppe Seyler. 1986 Feb;367(2):153-60
3964445
Biochim Biophys Acta. 1980 Dec 16;626(2):424-31
7213661
J Biol Chem. 1992 Aug 25;267(24):17248-56
1512262
Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14450-5
19667207
J Mol Biol. 2006 Feb 24;356(3):790-801
16403522
High Alt Med Biol. 2008 Summer;9(2):148-57
18578646
Respir Physiol Neurobiol. 2007 Sep 30;158(2-3):132-42
17561448
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11113-7
7972019
J Mol Biol. 1979 Apr 5;129(2):175-220
39173
Pediatr Res. 1979 Mar;13(3):167-9
471570
Biol Chem Hoppe Seyler. 1990 Jul;371(7):641-8
2222863
Biol Res. 2002;35(1):27-30
12125201
Nature. 1968 Jul 13;219(5150):131-9
5659637
Nature. 1970 Nov 21;228(5273):726-39
5528785
Acta Crystallogr D Biol Crystallogr. 2000 Jul;56(Pt 7):805-11
10930827