Unknown

Dataset Information

0

An Origin of Cooperative Oxygen Binding of Human Adult Hemoglobin: Different Roles of the ? and ? Subunits in the ?2?2 Tetramer.


ABSTRACT: Human hemoglobin (Hb), which is an ?2?2 tetramer and binds four O2 molecules, changes its O2-affinity from low to high as an increase of bound O2, that is characterized by 'cooperativity'. This property is indispensable for its function of O2 transfer from a lung to tissues and is accounted for in terms of T/R quaternary structure change, assuming the presence of a strain on the Fe-histidine (His) bond in the T state caused by the formation of hydrogen bonds at the subunit interfaces. However, the difference between the ? and ? subunits has been neglected. To investigate the different roles of the Fe-His(F8) bonds in the ? and ? subunits, we investigated cavity mutant Hbs in which the Fe-His(F8) in either ? or ? subunits was replaced by Fe-imidazole and F8-glycine. Thus, in cavity mutant Hbs, the movement of Fe upon O2-binding is detached from the movement of the F-helix, which is supposed to play a role of communication. Recombinant Hb (rHb)(?H87G), in which only the Fe-His in the ? subunits is replaced by Fe-imidazole, showed a biphasic O2-binding with no cooperativity, indicating the coexistence of two independent hemes with different O2-affinities. In contrast, rHb(?H92G), in which only the Fe-His in the ? subunits is replaced by Fe-imidazole, gave a simple high-affinity O2-binding curve with no cooperativity. Resonance Raman, 1H NMR, and near-UV circular dichroism measurements revealed that the quaternary structure change did not occur upon O2-binding to rHb(?H87G), but it did partially occur with O2-binding to rHb(?H92G). The quaternary structure of rHb(?H87G) appears to be frozen in T while its tertiary structure is changeable. Thus, the absence of the Fe-His bond in the ? subunit inhibits the T to R quaternary structure change upon O2-binding, but its absence in the ? subunit simply enhances the O2-affinity of ? subunit.

SUBMITTER: Nagatomo S 

PROVIDER: S-EPMC4526547 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

altmetric image

Publications

An Origin of Cooperative Oxygen Binding of Human Adult Hemoglobin: Different Roles of the α and β Subunits in the α2β2 Tetramer.

Nagatomo Shigenori S   Nagai Yukifumi Y   Aki Yayoi Y   Sakurai Hiroshi H   Imai Kiyohiro K   Mizusawa Naoki N   Ogura Takashi T   Kitagawa Teizo T   Nagai Masako M  

PloS one 20150805 8


Human hemoglobin (Hb), which is an α2β2 tetramer and binds four O2 molecules, changes its O2-affinity from low to high as an increase of bound O2, that is characterized by 'cooperativity'. This property is indispensable for its function of O2 transfer from a lung to tissues and is accounted for in terms of T/R quaternary structure change, assuming the presence of a strain on the Fe-histidine (His) bond in the T state caused by the formation of hydrogen bonds at the subunit interfaces. However, t  ...[more]

Similar Datasets

| S-EPMC9043147 | biostudies-literature
| S-EPMC8153241 | biostudies-literature
| S-EPMC18015 | biostudies-literature
| S-EPMC6287819 | biostudies-literature
| S-EPMC4353013 | biostudies-literature
| S-EPMC5383013 | biostudies-literature
| S-EPMC1904324 | biostudies-literature
| S-EPMC3707698 | biostudies-literature
| S-EPMC2144622 | biostudies-other
| S-EPMC6494993 | biostudies-literature