Erythropoietin and co.: intrinsic structure and functional disorder.
Erythropoietin (Epo) is a heavily glycosylated protein, with its main function being related to erythropoiesis, where it controls red blood cell production via interaction with the Epo receptor (EpoR). It also plays a number of important roles in various hormonal, growth factor, and cytokine pathways. These roles are defined by Epo partners, such as the homodimeric (EpoR)2 receptor, the heterodimeric EpoR/βCR receptor and hypoxia inducing factor (HIF). Although the main structural features of both Epo and EpoR are conserved in vertebrates, the secretion sites of Epo in mammals are different from those in other vertebrates. Both biosynthetic and synthetic analogues of this protein are available on the market. Several side effects, such as pure red cells aplaisa, increase the rate of cancer-related death in patients treated with recombinant Epo. The multifunctionality of Epo and the ability of this protein to serve as a hormone, a cytokine, and a growth factor suggest the presence of functional disorder, which is a typical "structural" feature of moonlighting proteins. The goal of this article is to evaluate the roles of intrinsic disorder in the functions of Epo and its primary interactors, EpoR, βCR, and HIF-1α.
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia. redwan1961@yahoo.com and Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia and Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. vuversky@health.usf.edu.
Vladimir N
VN
Uversky
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah, Saudi Arabia. redwan1961@yahoo.com and Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications, New Borg EL-Arab 21934, Alexandria, Egypt.
Elrashdy M
EM
Redwan
D000818:Animals; D004921:Erythropoietin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006031:Glycosylation; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D011485:Protein Binding; D017467:Receptors, Erythropoietin / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017467:Receptors, Erythropoietin; D004921:Erythropoietin