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A role of heme side-chains of human hemoglobin in its function revealed by circular dichroism and resonance Raman spectroscopy

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Abstract

Structural changes of heme side-chains of human adult hemoglobin (Hb A) upon ligand (O2 or CO) dissociation have been studied by circular dichroism (CD) and resonance Raman (RR) spectroscopies. We point out the occurrence of appreciable deformation of heme side-chains like vinyl and propionate groups prior to the out-of-plane displacement of heme iron. Referring to the recent fine resolved crystal structure of Hb A, the deformations of heme side-chains take place only in the β subunits. However, these changes are not observed in the isolated β chain (β4 homotetramer) and, therefore, are associated with the α–β inter-subunit interactions. For the communications between α and β subunits in Hb A regarding signals of ligand dissociation, possible routes are proposed on the basis of the time-resolved absorption, CD, MCD (magnetic CD), and RR spectroscopies. Our finding of the movements of heme side-chains would serve as one of the clues to solve the cooperative O2 binding mechanism of Hb A.

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Acknowledgements

We are grateful to the Japanese Red Cross Kanto-Koshinetsu Block Blood Center for the gift of concentrated red cells to advance this human hemoglobin study. 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) and Scientific Research (B) to T.K. (24350086), and also by a research grant from the Research Center for Micro-Nano Technology, Hosei University to M.N. and N.M.

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Authors and Affiliations

  1. Research Center for Micro-Nano Technology, Hosei University, Koganei, Tokyo, 184-0003, Japan

    Masako Nagai & Naoki Mizusawa

  2. School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, 920-0942, Japan

    Masako Nagai

  3. Picobiology Institute, Graduate School of Life Science, University of Hyogo, Ako-gun, Hyogo, 678-1297, Japan

    Teizo Kitagawa

  4. Department of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8571, Japan

    Shigenori Nagatomo

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  1. Masako Nagai
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  2. Naoki Mizusawa
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  4. Shigenori Nagatomo
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Correspondence to Masako Nagai.

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Masako Nagai declares that she has no conflict of interest. Naoki Mizusawa declares that he has no conflict of interest. Teizo Kitagawa declares that he has no conflict of interest. Shigenori Nagatomo declares that he has no conflict of interest.

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This article is part of a Special Issue on ‘Biomolecules to Bio-nanomachines - Fumio Arisaka 70th Birthday’ edited by Damien Hall, Junichi Takagi and Haruki Nakamura.

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Nagai, M., Mizusawa, N., Kitagawa, T. et al. A role of heme side-chains of human hemoglobin in its function revealed by circular dichroism and resonance Raman spectroscopy. Biophys Rev 10, 271–284 (2018). https://doi.org/10.1007/s12551-017-0364-5

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