ContentsGeneral DescriptionCytoglobin is the newest member of the globin family. This is due to its structural similarities with other members like Hemoglobin and Myoglobin as well as its internal heme iron group.
Cytoglobin is distributed widely throughout the body, particularly in fibroblast-like cells in splanchnic organs. It is thought that it might play a role in the fibrotic response in various organs, like the liver and kidneys[1]. This is evidenced by an increase in expression of CYGB expression in response to stressful stimuli including hypoxia and fibrotic stimulation[2]. CYGB has also been shown to inhibit cancer cell growth in vitro, suggesting it may have a role in tumor suppression[3]. However, it’s high affinity for oxygen suggest implications in oxygen sensing or signaling pathways. Overall, the definite function of Cytoglobin is still unknown but it’s structure gives rise to many theories as to what the many functions of the protein could be.
StructureCytoglobin is a 44.72 KDa protein, containing 190 amino acids[4]. The structure of Cytoglobin is largely alpha helices. The structure also contains a folding pattern characteristic of other globin-like proteins. It contains 8 alpha helices in a 3-over-3 sandwich conformation. CATH classifies each chain of the protein as 1.10.490.103[5]. The homodimer is stabilized by electrostatic interactions, hydrogen bonding, and an inter-subunit disulfide bridge at CYS38 and CYS832. The most highly conserved residues are the residues involved in the hydrophobic heme pocket, distal and proximal histidine residues, and the inter-subunit disulfide bridge. This is, once again, indicative of potential protein function[6]. Studies using immunoprecipitation/mass spectrometry did not find any interacting partners of cytoglobin[7]. Experiments conducted with high concentrations of CYGB have found that it was present only in the monomeric form[8].
Structural Insights into FunctionCytoglobin’s structure, particularly the heme group, contributes to its function greatly. In the deoxygenated form of cytoglobin, the heme group is coordinated with endogenous ligands at all 6 sites of the heme group, with the 6th site being occupied by a distal Histidine (His E7) residue on the protein. Oxygen competes with this His residue to bind CYGB[9].
CYGB also contains a disulfide bridge, which partially contributes to stabilizing the protein. This post-translational modification has indicated that the protein could be a redox sensitive protein. It is likely that a redox environment affects its interactions with gaseous ligands like oxygen, and thus affects its function. Experiments have shown that CYGB containing an intramolecular disulfide bridge has higher affinity for oxygen than the reduced form[10]. Evolutionarily Related ProteinsMyoglobin has very high homology, and it is suggested that CYGB emerged from a large scale duplication event[11].Hemoglobin also has high homology, with a query cover of 77% following a BLAST search using the Uniprot/SwissKB database[12].
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Updated on 12-July-2020
Myoglobin, Hemoglobin – hCYGB - human
1umo – hCYGB (mutant)
3ag0 – hCYGB + CO
1urv, 1ury, 1ut0, 1ux9 – hCYGB (mutant) + Fe(CN)6
4b3w – hCYGB (mutant) + CN + Fe(CN)6
6q6p – CYGB (mutant) – Antarctic toothfish
Dana M. Grass, Michal Harel, Alexander Berchansky, Joel L. Sussman
This page was last modified 06:47, 12 July 2020.