Abstract
This mini-review, mainly based on our resonance Raman studies on the structural origin of cooperative O2 binding in human adult hemoglobin (HbA), aims to answering why HbA is a tetramer consisting of two α and two β subunits. Here, we focus on the Fe-His bond, the sole coordination bond connecting heme to a globin. The Fe-His stretching frequencies reflect the O2 affinity and also the magnitude of strain imposed through globin by inter-subunit interactions, which is the origin of cooperativity. Cooperativity was first explained by Monod, Wyman, and Changeux, referred to as the MWC theory, but later explained by the two tertiary states (TTS) theory. Here, we related the higher-order structures of globin observed mainly by vibrational spectroscopy to the MWC theory. It became clear from the recent spectroscopic studies, X-ray crystallographic analysis, and mutagenesis experiments that the Fe-His bonds exhibit different roles between the α and β subunits. The absence of the Fe-His bond in the α subunit in some mutant and artificial Hbs inhibits T to R quaternary structural change upon O2 binding. However, its absence from the β subunit in mutant and artificial Hbs simply enhances the O2 affinity of the α subunit. Accordingly, the inter-subunit interactions between α and β subunits are nonsymmetric but substantial for HbA to perform cooperative O2 binding.
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Source: Nagai K, Kitagawa T, 1980
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We would like to thank Editage (www.editage.com) for English language editing.
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This study was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology for Scientific Research (C) to S.N. (17K05606), (20K03877) and Scientific Research (B) to T.K. (24350086), and by a research grant from the Research Center for Micro-Nano Technology, Hosei University, to M.N.
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Shigenori Nagatomo had the idea of the manuscript. The first draft of the manuscript was written by Teizo Kitagawa. Shigenori Nagatomo and Masako Nagai commented on the first draft of the manuscript. All authors read and approved the final manuscript.
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Nagatomo, S., Nagai, M. & Kitagawa, T. Structural origin of cooperativity in human hemoglobin: a view from different roles of α and β subunits in the α2β2 tetramer. Biophys Rev 14, 483–498 (2022). https://doi.org/10.1007/s12551-022-00945-7
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DOI: https://doi.org/10.1007/s12551-022-00945-7