Structure of the Altitude Adapted Hemoglobin of Guinea Pig in the R2-State

Pairet, Bruno; Jaenicke, Elmar

doi:10.1371/journal.pone.0012389

Cited by 15 publications

(13 citation statements)

References 35 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent findings suggest that Hb can access an ensemble of T states (Biswal & Vijayan, 2002). Several quaternary states of liganded Hb such as relaxed (R), R2, B and Y have also been reported in the literature (Silva et al, 1992;Smith & Simmons, 1994;Kroeger & Kundrot, 1997;Schumacher et al, 1997;Pairet & Jaenicke, 2010). In this work, we will restrict our discussion to the R and R2 states of Hb.…”

Section: Introductionmentioning

confidence: 82%

Structure of Greyhound hemoglobin: origin of high oxygen affinity

Bhatt

Zaldívar‐López

Harris

et al. 2011

Acta Crystallogr D Biol Cryst

View full text Add to dashboard Cite

This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.

show abstract

Section: Introductionmentioning

confidence: 82%

Structure of Greyhound hemoglobin: origin of high oxygen affinity

Bhatt

Zaldívar‐López

Harris

et al. 2011

Acta Crystallogr D Biol Cryst

View full text Add to dashboard Cite

show abstract

“…The highland hemoglobin variant has a looser α 1 β 2 /α 2 β 1 switch region than the lowland variant due to the α50 mutation, and the nature of atomic contacts at the α 1 β 1 interface is also different because of mutations at β128, α113, α115 and α116. In guinea pig hemoglobin [38], the lack of a salt bridge between αThr30 and αPro50 conferred an increased flexibility. Also, the guinea pig hemoglobin has αHis40 instead of αPro40 (as in human hemoglobin), and the bulkiness of histidine affects the α 1 β 2 /α 2 β 1 interface during the T↔R transition in quaternary structure.…”

Section: Discussionmentioning

confidence: 99%

Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

Inoguchi¹,

Mizuno²,

Baba³

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

BackgroundDeer mice (Peromyscus maniculatus) that are native to high altitudes in the Rocky Mountains have evolved hemoglobins with an increased oxygen-binding affinity relative to those of lowland conspecifics. To elucidate the molecular mechanisms responsible for the evolved increase in hemoglobin-oxygen affinity, the crystal structure of the highland hemoglobin variant was solved and compared with the previously reported structure for the lowland variant.ResultsHighland hemoglobin yielded at least two crystal types, in which the longest axes were 507 and 230 Å. Using the smaller unit cell crystal, the structure was solved at 2.2 Å resolution. The asymmetric unit contained two tetrameric hemoglobin molecules.ConclusionsThe analyses revealed that αPro50 in the highland hemoglobin variant promoted a stable interaction between αHis45 and heme that was not seen in the αHis50 lowland variant. The αPro50 mutation also altered the nature of atomic contacts at the α1β2/α2β1 intersubunit interfaces. These results demonstrate how affinity-altering changes in intersubunit interactions can be produced by mutations at structurally remote sites.

show abstract

“…Hemoglobin varies among animal species in its sequence, its oxygen-binding and its regulation by small molecules (Perutz, 1983). The structural variation in hemoglobins and increased affinity for oxygen have been correlated with such factors as species habitats and lifestyles such as high altitude environments for llama, guinea pigs and other Andean species (Perutz, 1983;Jessen et al, 1991;Storz, 2007;Storz and Moriyama, 2008;Painet and Jaenicke, 2010). Increased affinity for oxygen for some hemoglobins is also correlated with high altitude flight for vultures and black headed gull, bar headed goose and Andean geese (Hieblet al, 1988;Godovac-Zimmermann et al, 1988;Jessen et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Conservation of Binding of Llama and Other Animals’ Hemoglobins to Haptoglobins Across Species

Woldemeskel¹,

Vanderpuye²

2018

American Journal of Biochemistry and Biotechnology

View full text Add to dashboard Cite

The plasma protein haptoglobin binds hemoglobin released from lysed erythrocytes. It causes removal of the free hemoglobin, thus preventing pathological oxidation of cells. Hemoglobin higher level structures are well conserved across animal species but primary structures can be as little as 50% homologous. Because of these differences, the question arose as to what extent hemoglobins can bind to haptoglobins from different species. The charge properties and binding to three genetic variants of human haptoglobin were compared by non-denaturing agarose gel electrophoresis, with llama, human, dog, pig, horse and goat hemoglobins. In this study, it was reported for the first time that llama and alpaca hemoglobins differed in electrophoretic mobility from hemoglobins from several animal species and humans. Llama hemoglobin was more positively charged than the other mammalian hemoglobins. Electrophoretic mobility changes of the animal hemoglobins in the presence of human plasma and two different purified human haptoglobin genetic variants suggested that hemoglobins from all animals in this study could bind all three genetic variants of human haptoglobin. In all cases, the llama hemoglobin-haptoglobin samples had lesser mobility than those of the other mammals. This study showed that the binding sites on hemoglobin and haptoglobin for each other have been evolutionarily conserved despite differences in primary structure and marked difference in the charge of llama hemoglobin from the other animal species and humans.

show abstract

Structure of the Altitude Adapted Hemoglobin of Guinea Pig in the R2-State

Cited by 15 publications

References 35 publications

Structure of Greyhound hemoglobin: origin of high oxygen affinity

Structure of Greyhound hemoglobin: origin of high oxygen affinity

Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

Conservation of Binding of Llama and Other Animals’ Hemoglobins to Haptoglobins Across Species

Contact Info

Product

Resources

About