ZFIN ID: ZDB-PUB-180206-13
Globin X is a six-coordinate globin that reduces nitrite to nitric oxide in fish red blood cells
Corti, P., Xue, J., Tejero, J., Wajih, N., Sun, M., Stolz, D.B., Tsang, M., Kim-Shapiro, D.B., Gladwin, M.T.
Date: 2016
Source: Proceedings of the National Academy of Sciences of the United States of America   113: 8538-43 (Journal)
Registered Authors: Tsang, Michael
Keywords: RBC, blood, nitric oxide, nitrite, platelet
MeSH Terms:
  • Animals
  • Cells, Cultured
  • Electron Transport
  • Erythrocytes/cytology
  • Erythrocytes/metabolism*
  • Fishes/blood
  • Fishes/genetics
  • Fishes/metabolism*
  • Gene Expression
  • Globins/genetics
  • Globins/metabolism*
  • Hemoglobins/genetics
  • Hemoglobins/metabolism
  • Humans
  • Nitric Oxide/metabolism*
  • Nitrites/metabolism*
  • Oxidation-Reduction
  • RNA Interference
  • Zebrafish/blood
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed: 27407144 Full text @ Proc. Natl. Acad. Sci. USA
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ABSTRACT
The discovery of novel globins in diverse organisms has stimulated intense interest in their evolved function, beyond oxygen binding. Globin X (GbX) is a protein found in fish, amphibians, and reptiles that diverged from a common ancestor of mammalian hemoglobins and myoglobins. Like mammalian neuroglobin, GbX was first designated as a neuronal globin in fish and exhibits six-coordinate heme geometry, suggesting a role in intracellular electron transfer reactions rather than oxygen binding. Here, we report that GbX to our knowledge is the first six-coordinate globin and the first globin protein apart from hemoglobin, found in vertebrate RBCs. GbX is present in fish erythrocytes and exhibits a nitrite reduction rate up to 200-fold faster than human hemoglobin and up to 50-fold higher than neuroglobin or cytoglobin. Deoxygenated GbX reduces nitrite to form nitric oxide (NO) and potently inhibits platelet activation in vitro, to a greater extent than hemoglobin. Fish RBCs also reduce nitrite to NO and inhibit platelet activation to a greater extent than human RBCs, whereas GbX knockdown inhibits this nitrite-dependent NO signaling. The description of a novel, six-coordinate globin in RBCs with dominant electron transfer and nitrite reduction functionality provides new insights into the evolved signaling properties of ancestral heme-globins.
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