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Functionality of intrinsic disorder in tumor necrosis factor‐α and its receptors
Author(s) -
Uversky Vladimir N.,
ElBaky Nawal Abd,
ElFakharany Esmail M.,
Sabry Amira,
Mattar Ehab H.,
Uversky Alexey V.,
Redwan Elrashdy M.
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14182
Subject(s) - receptor , tumor necrosis factor alpha , cytokine , biology , cytoplasm , microbiology and biotechnology , cytokine receptor , zebrafish , peptide sequence , genetics , immunology , gene
Tumor necrosis factor‐α ( TNF ‐α) is a pleiotropic inflammatory cytokine that exerts potent cytotoxic effects on solid tumor cells, while not affecting their normal counterparts. It is also known that TNF ‐α exerts many of its biological functions via interaction with specific receptors. To understand the potential roles of intrinsic disorder in the functioning of this important cytokine, we explored the peculiarities of intrinsic disorder distribution in human TNF ‐α and its homologs from various species, ranging from zebrafish to chimpanzee. We also studied the peculiarities of intrinsic disorder distribution in human TNF ‐α receptors, TNFR 1 and TNFR 2. Analysis revealed that cytoplasmic domains of TNF ‐α and its receptors are expected to be highly disordered. Furthermore, although the sequence identities of analyzed TNF ‐α homologs range from 99.57% (between human and chimpanzee proteins) to 22.33% (between frog and fish proteins), their intrinsic disorder profiles are characterized by a remarkable similarity. These observations indicate that the peculiarities of distribution of the intrinsic disorder propensity within the amino acid sequences are evolutionary conserved, and therefore could be of functional importance for this family of proteins. We also show that disordered and flexible regions of human TNF ‐α and its TNFR 1 and TNFR 2 receptors are crucial for some of their biological activities.