PMID- 28746777
OWN - NLM
STAT- MEDLINE
DCOM- 20171124
LR  - 20180320
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Linking)
VI  - 284
IP  - 21
DP  - 2017 Nov
TI  - Functionality of intrinsic disorder in tumor necrosis factor-alpha and its receptors.
PG  - 3589-3618
LID - 10.1111/febs.14182 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha and 
      its homologs from various species, ranging from zebrafish to chimpanzee. We also 
      studied the peculiarities of intrinsic disorder distribution in human TNF-alpha 
      receptors, TNFR1 and TNFR2. Analysis revealed that cytoplasmic domains of TNF-alpha 
      and its receptors are expected to be highly disordered. Furthermore, although the 
      sequence identities of analyzed TNF-alpha 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-alpha and its TNFR1 and 
      TNFR2 receptors are crucial for some of their biological activities.
CI  - (c) 2017 Federation of European Biochemical Societies.
FAU - Uversky, Vladimir N
AU  - Uversky VN
AD  - Department of Biological Sciences, Faculty of Sciences, King Abdulaziz 
      University, Jeddah, Saudi Arabia.
AD  - Department of Molecular Medicine and USF Health Byrd Alzheimer's Research 
      Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 
      USA.
AD  - Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, 
      Moscow Region, Russia.
FAU - El-Baky, Nawal Abd
AU  - El-Baky NA
AD  - Protective Proteins Laboratory, Protein Research Department, Genetic Engineering 
      and Biotechnology Research Institute, City for Scientific Research and Technology 
      Applications, New Borg EL-Arab, Alexandria, Egypt.
FAU - El-Fakharany, Esmail M
AU  - El-Fakharany EM
AD  - Protective Proteins Laboratory, Protein Research Department, Genetic Engineering 
      and Biotechnology Research Institute, City for Scientific Research and Technology 
      Applications, New Borg EL-Arab, Alexandria, Egypt.
FAU - Sabry, Amira
AU  - Sabry A
AD  - Protective Proteins Laboratory, Protein Research Department, Genetic Engineering 
      and Biotechnology Research Institute, City for Scientific Research and Technology 
      Applications, New Borg EL-Arab, Alexandria, Egypt.
FAU - Mattar, Ehab H
AU  - Mattar EH
AD  - Department of Biological Sciences, Faculty of Sciences, King Abdulaziz 
      University, Jeddah, Saudi Arabia.
FAU - Uversky, Alexey V
AU  - Uversky AV
AD  - Center for Data Analytics and Biomedical Informatics, Department of Computer and 
      Information Sciences, College of Science and Technology, Temple University, 
      Philadelphia, PA, USA.
FAU - Redwan, Elrashdy M
AU  - Redwan EM
AD  - Department of Biological Sciences, Faculty of Sciences, King Abdulaziz 
      University, Jeddah, Saudi Arabia.
AD  - Protective Proteins Laboratory, Protein Research Department, Genetic Engineering 
      and Biotechnology Research Institute, City for Scientific Research and Technology 
      Applications, New Borg EL-Arab, Alexandria, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20170816
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Databases, Genetic
MH  - Humans
MH  - Receptors, Tumor Necrosis Factor/*chemistry/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*chemistry/genetics/*metabolism
OTO - NOTNLM
OT  - cytokine
OT  - intrinsic disorder
OT  - intrinsically disordered protein
OT  - post-translational modifications
OT  - protein-protein interactions
OT  - tumor necrosis factor-alpha
EDAT- 2017/07/27 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/07/27 06:00
PHST- 2017/04/03 00:00 [received]
PHST- 2017/06/15 00:00 [revised]
PHST- 2017/07/20 00:00 [accepted]
PHST- 2017/07/27 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/07/27 06:00 [entrez]
AID - 10.1111/febs.14182 [doi]
PST - ppublish
SO  - FEBS J. 2017 Nov;284(21):3589-3618. doi: 10.1111/febs.14182. Epub 2017 Aug 16.