Cytoglobin is a globin molecule ubiquitously expressed in all tissues and most notably utilized in marine mammals. It was discovered in 2001[6] in hepatic stellate cells during liver fibrosis. Thus, it was originally called "stellate cell activated protein" or STAP.[7] It received its current name in 2002.[8] It is thought to help in the distribution and storage of oxygen as well as protect against hypoxia by scavenging reactive oxygen species . The predicted function of cytoglobin is the facilitation of oxygen among tissues that don't express myoglobin.[9]
Cytoglobin has 30-40% sequence homology with myoglobin, and has a similar oxygen binding affinity. One of the major differences is the presence of a 20 amino acids extension at both the n and c terminus.[11]
Cytoglobin is a hexacoordinate heme protein. The heme iron in coordinated with histidine residues on both sides, HisF8 and HisE7. The HisE7 is considered to be an "endogenous ligand." In order for oxygen or another gaseous ligand to bind, the HisE7 must dissociate from the iron, making the binding kinetics relatively slow.[12]
Diagram of how the heme group in cytoglobin interacts with the surrounding amino acids of the globin protein. Normally, the iron is coordinated with histidine residues on both sides. The HisE7 must be dissociated in order for oxygen to bind.
In an oxidizing environment, a disulfide bond between Cys38 and Cys83 of the protein forms and causes a conformational change to move HisE7 out of the way, allowing oxygen to bind. Thus, oxygen binding is dependent on the redox state of the tissue.[11]
Applications
CYGB expression can be used as a specific marker with which hepatic stellate cells can be distinguished from portal myofibroblasts in the damaged human liver.[13]
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Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y (May 2003). "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans". Biochemistry. 42 (17): 5133–42. doi:10.1021/bi027067e. PMID12718557.
Hünermund G, Schirmacher A, Ringelstein B, Young P, Watts GD, Meuleman J, Nelis E, Chance PF, Timmerman V, Stögbauer F, Kuhlenbäumer G (Apr 2004). "Genomic organization and mutation analysis of three candidate genes for hereditary neuralgic amyotrophy". Muscle & Nerve. 29 (4): 601–4. doi:10.1002/mus.20009. PMID15052627. S2CID39945876.
de Sanctis D, Dewilde S, Pesce A, Moens L, Ascenzi P, Hankeln T, Burmester T, Bolognesi M (Feb 2004). "Crystal structure of cytoglobin: the fourth globin type discovered in man displays heme hexa-coordination". Journal of Molecular Biology. 336 (4): 917–27. doi:10.1016/j.jmb.2003.12.063. PMID15095869. S2CID21144924.
Sugimoto H, Makino M, Sawai H, Kawada N, Yoshizato K, Shiro Y (Jun 2004). "Structural basis of human cytoglobin for ligand binding". Journal of Molecular Biology. 339 (4): 873–85. doi:10.1016/j.jmb.2004.04.024. PMID15165856.
Sawai H, Makino M, Mizutani Y, Ohta T, Sugimoto H, Uno T, Kawada N, Yoshizato K, Kitagawa T, Shiro Y (Oct 2005). "Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin". Biochemistry. 44 (40): 13257–65. doi:10.1021/bi050997o. PMID16201751.
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