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.
- Proceedings of the National Academy of Sciences of the United States of America 113: 8538-43 (Journal)
- Registered Authors
- Tsang, Michael
- RBC, blood, nitric oxide, nitrite, platelet
- MeSH Terms
- Cells, Cultured
- Electron Transport
- Gene Expression
- Nitric Oxide/metabolism*
- RNA Interference
- 27407144 Full text @ Proc. Natl. Acad. Sci. USA
Corti, P., Xue, J., Tejero, J., Wajih, N., Sun, M., Stolz, D.B., Tsang, M., Kim-Shapiro, D.B., Gladwin, M.T. (2016) Globin X is a six-coordinate globin that reduces nitrite to nitric oxide in fish red blood cells. Proceedings of the National Academy of Sciences of the United States of America. 113:8538-43.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes