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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Insights into Evolutionary and Conservancy Analytics on Human Insulin Receptor Proteins

Author(s): Chidhambara Priya Dharshini Kottaisamy, Divya S. Raj and Manish Dwivedi*

Volume 20, Issue 5, 2023

Published on: 11 August, 2022

Page: [536 - 544] Pages: 9

DOI: 10.2174/1570180819666220510140605

Price: $65

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Abstract

Background: The insulin receptor protein of humans is proposed to have substantial application in the regulatory pathway of glucose levels in the blood. The cellular function of the insulin hormone is initiated by its association with the insulin receptor (IR) protein, and this process is common to most vertebrate species. Thus, phylogenetic analysis of IR protein among various associated species in vertebrates can elucidate the importance of residues and structure, and the relationship with its function as the conserved region of residues is associated with evolutionary conservation on insulin receptor proteins. In the present study, we have used various in silico approaches and conducted the phylogenetic analysis.

Methods: The basic local alignment search tool (BLAST) was employed to screen the 250 vertebrates. After evolutionary analysis, Pan troglodytes (Chimpanzees) have been observed as the closest relatives of Homo sapiens concerning insulin receptor proteins.

Results: Human insulin receptor protein was found to have hydrophobic nature by hydrophobicity profile analysis, where most of the positions were above the mean hydrophobicity value from n-terminal to cterminal residues, whereas carboxy-terminal residues were observed as hydrophilic. High entropy was observed at the short stretch at N-terminal, C-terminal, and a linker region within the alignment, but the overall positions which were aligned showed low entropic regions.

Conclusion: The outcomes of this work have revealed some unexplored specific characteristics of the conserved domains among different taxa of selected vertebrates and have also illustrated the hierarchical assemblage-based inconsistent variation of the IR proteins, and further conservancy analysis discloses the significance of each site for protein structure or function.

Keywords: Insulin receptor, phylogenetic, hydrophobicity, entropy, alignment, vertebrates.

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[1]
Röder, P.V.; Wu, B.; Liu, Y.; Han, W. Pancreatic regulation of glucose homeostasis. Exp. Mol. Med., 2016, 48(3), e219.
[http://dx.doi.org/10.1038/emm.2016.6] [PMID: 26964835]
[2]
Hubbard, S.R.; Wei, L.; Ellis, L.; Hendrickson, W.A. Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature, 1994, 372(6508), 746-754.
[http://dx.doi.org/10.1038/372746a0] [PMID: 7997262]
[3]
Hubbard, S.R. Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog. EMBO J., 1997, 16(18), 5572-5581.
[http://dx.doi.org/10.1093/emboj/16.18.5572] [PMID: 9312016]
[4]
De Meyts, P. The insulin receptor: A prototype for dimeric, allosteric membrane receptors? Trends Biochem. Sci., 2008, 33(8), 376-384.
[http://dx.doi.org/10.1016/j.tibs.2008.06.003] [PMID: 18640841]
[5]
Boucher, J.; Kleinridders, A.; Kahn, C.R. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb. Perspect. Biol., 2014, 6(1), a009191.
[http://dx.doi.org/10.1101/cshperspect.a009191] [PMID: 24384568]
[6]
De Meyts, P. The insulin receptor and its signal transduction network, in endotext.South Dartmouth (MA) , 2000. pp. K.R. Feingold, et al., Editors2000-2022.
[7]
Fu, Z.; Gilbert, E.R.; Liu, D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr. Diabetes Rev., 2013, 9(1), 25-53.
[http://dx.doi.org/10.2174/157339913804143225] [PMID: 22974359]
[8]
Escribano, O.; Beneit, N.; Rubio-Longás, C.; López-Pastor, A.R.; Gómez-Hernández, A. The role of insulin receptor isoforms in diabetes and its metabolic and vascular complications. J. Diabetes Res., 2017, 2017, 1403206.
[http://dx.doi.org/10.1155/2017/1403206] [PMID: 29201918]
[9]
Wilcox, G. Insulin and insulin resistance. Clin. Biochem. Rev., 2005, 26(2), 19-39.
[PMID: 16278749]
[10]
Virkamäki, A.; Ueki, K.; Kahn, C.R. Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J. Clin. Invest., 1999, 103(7), 931-943.
[http://dx.doi.org/10.1172/JCI6609] [PMID: 10194465]
[11]
Vella, F. Introduction to protein structure. By C Branden and J Tooze. In: Biochem; Educ; garland publishing: New York, 1992; 20, pp. (2)121-122.
[http://dx.doi.org/10.1016/0307-4412(92)90131-5]
[12]
Ashkenazy, H.; Erez, E.; Martz, E.; Pupko, T.; Ben-Tal, N. ConSurf 2010: Calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. In: Nucleic Acids Res; , 2010; 38, pp. (Web Server issue)W529-33.
[13]
Chenna, R.; Sugawara, H.; Koike, T.; Lopez, R.; Gibson, T.J.; Higgins, D.G.; Thompson, J.D. Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res., 2003, 31(13), 3497-3500.
[http://dx.doi.org/10.1093/nar/gkg500] [PMID: 12824352]
[14]
Alzohairy, A. BioEdit: An important software for molecular biology. GERF Bull. Biosci., 2011, 2, 60-61.
[15]
Hall, T.A. BioEdit: A user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl. Acids. Symp. Ser., 1999, 41, 95-98.
[16]
Kyte, J.; Doolittle, R.F. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol., 1982, 157(1), 105-132.
[http://dx.doi.org/10.1016/0022-2836(82)90515-0] [PMID: 7108955]
[17]
Kumar, S.; Stecher, G.; Li, M.; Knyaz, C.; Tamura, K. MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol., 2018, 35(6), 1547-1549.
[http://dx.doi.org/10.1093/molbev/msy096] [PMID: 29722887]
[18]
Altschul, S.F.; Gish, W. Local alignment statistics. Methods Enzymol., 1996, 266, 460-480.
[http://dx.doi.org/10.1016/S0076-6879(96)66029-7] [PMID: 8743700]
[19]
Felsenstein, J. Confidence limits on phylogenies: An approach using the bootstrap. Evolution, 1985, 39(4), 783-791.
[http://dx.doi.org/10.1111/j.1558-5646.1985.tb00420.x] [PMID: 28561359]
[20]
Zuckerkandl, E.; Pauling, L. Evolutionary Divergence and Convergence in Proteins. Evolving Genes and Proteins; Bryson, V; Vogel, H.J., Ed.; Academic Press, 1965, pp. 97-166.
[http://dx.doi.org/10.1016/B978-1-4832-2734-4.50017-6]
[21]
Saitou, N.; Nei, M. The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol. Biol. Evol., 1987, 4(4), 406-425.
[PMID: 3447015]
[22]
Seino, S.; Seino, M.; Nishi, S.; Bell, G.I. Structure of the human insulin receptor gene and characterization of its promoter. Proc. Natl. Acad. Sci. USA, 1989, 86(1), 114-118.
[http://dx.doi.org/10.1073/pnas.86.1.114] [PMID: 2911561]
[23]
Kido, Y.; Nakae, J.; Accili, D. Clinical review 125: The insulin receptor and its cellular targets. J. Clin. Endocrinol. Metab., 2001, 86(3), 972-979.
[PMID: 11238471]
[24]
Czech, M.P. The nature and regulation of the insulin receptor: Structure and function. Annu. Rev. Physiol., 1985, 47, 357-381.
[http://dx.doi.org/10.1146/annurev.ph.47.030185.002041] [PMID: 2986534]
[25]
Hubbard, S.R. The insulin receptor: Both a prototypical and atypical receptor tyrosine kinase. Cold Spring Harb. Perspect. Biol., 2013, 5(3), a008946.
[http://dx.doi.org/10.1101/cshperspect.a008946] [PMID: 23457259]
[26]
Cabail, M.Z.; Li, S.; Lemmon, E.; Bowen, M.E.; Hubbard, S.R.; Miller, W.T. The insulin and IGF1 receptor kinase domains are functional dimers in the activated state. Nat. Commun., 2015, 6, 6406.
[http://dx.doi.org/10.1038/ncomms7406] [PMID: 25758790]
[27]
Schrödinger, L.; DeLano, W. PyMOL. Retrieved from; , 2020. Available: http://www.pymol.org/pymol
[28]
Lee, J.; Pilch, P.F. The insulin receptor: Structure, function, and signaling. Am. J. Physiol., 1994, 266(2 Pt 1), C319-C334.
[http://dx.doi.org/10.1152/ajpcell.1994.266.2.C319] [PMID: 8141246]
[29]
Al-Salam, A.; Irwin, D.M. Evolution of the vertebrate insulin receptor substrate (Irs) gene family. BMC Evol. Biol., 2017, 17(1), 148.
[http://dx.doi.org/10.1186/s12862-017-0994-z] [PMID: 28645244]
[30]
Hernández-Sánchez, C.; Mansilla, A.; de Pablo, F.; Zardoya, R. Evolution of the insulin receptor family and receptor isoform expression in vertebrates. Mol. Biol. Evol., 2008, 25(6), 1043-1053.
[http://dx.doi.org/10.1093/molbev/msn036] [PMID: 18310661]
[31]
Cover, T.M.; Thomas, J.A. Elements of Information Theory; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2005.
[http://dx.doi.org/10.1002/047174882X]
[32]
Ebeling, W. Physical Approaches to Biological Evolution; Springer: Berlin/Heidelberg, Germany, 2011, Vol. 191, pp. 142-143.
[33]
Müller, I. A History of Thermodynamics: The Doctrine of Energy and Entropy; Springer: Berlin/Heidelberg, Germany, 2007.
[34]
Gibbs, J.W. Elementary Principles in Statistical Mechanics; Gale: New York, NY, USA, 1902.
[35]
Boltzmann, L. Über die Beziehung eines allgemeinen mechanischen Satzes zum zweiten Hauptsatze der Wärmetheorie. 1970. (In German)
[http://dx.doi.org/10.1007/978-3-322-84986-1_5]

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