Cited by 274Hemoglobin structure and functionHeme Oxygenase-1 and Carbon MonoxideMetal-Catalyzed Oxygenation Mechanisms

The redox state of the cell regulates the ligand binding affinity of human neuroglobin and cytoglobin

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Hamdane, Djemel, Kiger, Laurent, Dewilde, Sylvia, Green, Brian N., Pesce, Alessandra, Uzan, Julien, Burmester, Thorsten, Hankeln, Thomas +3 more·2003·Journal of Biological Chemistry

Abstract

Neuroglobin and cytoglobin reversibly bind oxygen in competition with the distal histidine, and the observed oxygen affinity therefore depends on the properties of both ligands. In the absence of an external ligand, the iron atom of these globins is hexacoordinated. There are three cysteine residues in human neuroglobin; those at positions CD7 and D5 are sufficiently close to form an internal disulfide bond. Both cysteine residues in cytoglobin, although localized in other positions than in human neuroglobin, may form a disulfide bond as well. The existence and position of these disulfide bonds was demonstrated by mass spectrometry and thiol accessibility studies. Mutation of the cysteines involved, or the use of reducing agents to break the S-S bond, led to a decrease in the observed oxygen affinity of human neuroglobin by an order of magnitude. The critical parameter is the histidine dissociation rate, which changes by about a factor of 10. The same effect is observed with human cytoglobin, although to a much lesser extent (less than a factor of 2). These results suggest a novel mechanism for the regulation of oxygen binding; contact with an appropriate electron donor would provoke the release of oxygen. Hence the oxygen affinity would be directly linked to the redox state of the cell.

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  1. Watts, R. A., Hunt, P. W., Hvitved, A. N., Hargrove, M. S., Peacock, W. J., and Dennis, E. S. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 10119 -10124
  2. Sun, Y., Jin, K., Peel, A., Mao, X. O., Xie, L., and Greenberg, D. A. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 3497-3500
  3. Sun, Y., Jin, K., Mao, X. O., Zhu, Y., and Greenberg, D. A. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 15306 -15311
  4. Kriegl, J. M., Bhattacharyya, A. J., Nienhaus, K., Deng, P., Minkow, O., and Nienhaus, G. U. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 7992-7997
  5. Royer, W. E., Jr., Strand, K., van Heel, M., and Hendrickson, W. A. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 7107-7111

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Authors
Hamdane, D., Kiger, L., Dewilde, S., Green, B. N., Pesce, A., Uzan, J., Burmester, T., Hankeln, T., Bolognesi, M., Moens, L., & Marden, M. C.
Affiliations
  • Inserm (FR)
  • University of Antwerp (BE)
  • University of Genoa (IT)
  • Johannes Gutenberg University Mainz (DE)
Corresponding author
Marden, Michael C.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-12
Volume
278
Issue
51
Pages
51713-51721
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2164923948
Cited by
274
References
38
Citations by year
2026: 3 · 2025: 11 · 2024: 3 · 2023: 11 · 2022: 10 · 2021: 8 · 2020: 8 · 2019: 8 · 2018: 11 · 2017: 14 · 2016: 13 · 2015: 12 · 2014: 11 · 2013: 15 · 2012: 8
FWCI
5.22
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, cc-by)
Funders
  • European Commission (QLG3-CT-2002-01548)
  • Deutsche Forschungsgemeinschaft (Ha2103/3, Bu956/5)
  • Institut National de la Santé et de la Recherche Médicale
  • Consiglio Nazionale delle Ricerche
  • Universiteit Antwerpen
  • Vlaamse regering
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
  • Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
Keywords
neuroglobin, cytoglobin, oxygen affinity, redox regulation, disulfide bonds, cysteine residues, distal histidine, reducing agents, electron donors
MeSH terms
Neuroglobin, Cytoglobin, Cysteine, Disulfides, Globins, Histidine, Humans, Kinetics, Ligands, Models, Molecular, Nerve Tissue Proteins, Oxidation-Reduction, Oxygen, Protein Binding, Recombinant Proteins, Spectrometry, Mass, Electrospray Ionization

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