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Homology Modelling of Chemerin like Receptor-1 (CMKLR1): Potential Target for Treating Type II Diabetes

  • B, Sathya. (Department of Genetic Engineering, School of Bioengineering, SRM University)
  • 투고 : 2017.02.01
  • 심사 : 2017.03.25
  • 발행 : 2017.03.30

초록

Chemerin receptor, which predominantly expressed in immune cells as well as adipose tissue, was found to stimulate chemotaxis of dendritic cells and macrophages to the site of inflammation. Chemerin is a widely distributed multifunctional secreted protein implicated in immune cell migration, adipogenesis, osteoblastogenesis, angiogenesis, myogenesis, and glucose homeostasis. Recent studies suggest chemerin may play an important role in the pathogenesis of obesity and insulin resistance and it becomes a potential therapeutic target for treating type II diabetes. The crystal structure of chemerin receptor has not yet been resolved. Therefore, in the present study, homology modelling of CMKLR1 was done utilizing the crystal structure of human angiotension receptor in complex with inverse agonist olmesartan as the template. Since the template has low sequence identity, we have incorporated both threading and comparative modelling approach to generate the three dimensional structure. 3D models were generated and validated. The reported models can be used to characterize the critical amino acid residues in the binding site of CMKLR1.

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참고문헌

  1. S. Nagpal, S. Patel, H. Jacobe, D. DiSepio, C. Ghosn, M. Malhotra, M. Teng, M. Duvic, and R. A. Chandraratna, "Tazarotene-induced gene2 (TIG2), a novel retinoid-responsive gene in skin", J. Invest. Dermatol., Vol. 109, pp.91-95, 1997. https://doi.org/10.1111/1523-1747.ep12276660
  2. W. Meder, M. Wendland, A. Busmann, C. Kutzleb, N. Spodsberg, H. John, R. Richter, D. Schleuder, M. Meyer, and W. G. Forssmann, "Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23", FEBS Lett., Vol. 555, pp. 495-499, 2003. https://doi.org/10.1016/S0014-5793(03)01312-7
  3. B. A. Zabel, S. J. Allen, P. Kulig, J. A. Allen, J. Cichy, T. M. Handel, and E. C. Butcher, "Chemerin activation by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades", J. Biol. Chem., Vol. 280, pp. 34661-34666, 2005. https://doi.org/10.1074/jbc.M504868200
  4. S. Schultz, A. Saalbach, J. T. Heiker, R. Meier, T. Zellmann, J. C. Simon, and A. G. Beck-Sickinger, "Proteolytic activation of prochemerin by kallikrein 7 breaks an ionic linkage and results in C-terminal rearrangement", Biochem. J., Vol. 452, pp. 271-280, 2013. https://doi.org/10.1042/BJ20121880
  5. S.-G. Roh, S.-H. Song, K.-C. Choi, K. Katoh, V. Wittamer, M. Parmentier, and S. Sasakim, "Chemerin-a new adipokine that modulates adipogenesis via its own receptor", Biochem. Bioph. Res. Co., Vol. 362, pp. 1013-1018, 2007. https://doi.org/10.1016/j.bbrc.2007.08.104
  6. M. Samson, A. L. Edinger, P. Stordeur, J. Rucker, V. Verhasselt, M. Sharron, C. Govaerts, C. Mollereau, G. Vassart, R. W. Doms, and M. Parmentier, "Chem23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-2 strains", Eur. J. Immunol., Vol. 28, pp. 1689-1700, 1998. https://doi.org/10.1002/(SICI)1521-4141(199805)28:05<1689::AID-IMMU1689>3.0.CO;2-I
  7. A. E. Adams, Y. Abu-Amer, J. Chappel, S. Stueckle, F. P. Ross, S. L. Teitelbaum, and L. J. Suva "1,25 dihydroxyvitamin D3 and dexamethasone induce the cyclooxygenase 1 gene in osteoclast-supporting stromal cells", J. Cell. Biochem., Vol. 74, pp. 587-595, 1999. https://doi.org/10.1002/(SICI)1097-4644(19990915)74:4<587::AID-JCB8>3.0.CO;2-G
  8. S. Parolini, A. Santoro, E. Marcenaro, W. Luini, L. Massardi, F. Facchetti, D. Communi, M. Parmentier, A. Majorana, M. Sironi, G. Tabellini, A. Moretta, and S. Sozzani, "The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues", Blood, Vol.109, pp. 3625-3632, 2007. https://doi.org/10.1182/blood-2006-08-038844
  9. V. Wittamer, J. D. Franssen, M. Vulcano, J. F. Mir jolet, E. Le Poul, I. Migeotte, S. Brezillon, R. Tyldesley, C. Blanpain, M. Detheux, A. Mantovani, S. Sozzani, G. Vassart, M. Parmentier, and D. Communi, "Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids", J. Exp. Med., Vol. 198, pp. 977-985, 2003. https://doi.org/10.1084/jem.20030382
  10. K. Bozaoglu, K. Bolton, J. McMillan, P. Zimmet, J. Jowett, G. Collier, K. Walder, and D. Segal, "Chemerin is a novel adipokine associated with obesity and metabolic syndrome", Endocrinology, Vol.148, pp. 4687-4694, 2007. https://doi.org/10.1210/en.2007-0175
  11. K. B. Goralski, T. C. McCarthy, E. A. Hanniman, B. A. Zabel, E. C. Butcher, S. D. Parlee, S. Muruganandan, and C. J. Sinal, "Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism", J. Biol. Chem., Vol. 282, pp. 28175-28188, 2007. https://doi.org/10.1074/jbc.M700793200
  12. H. Xu, G. T. Barnes, Q. Yang, G. Tan, D. Yang, C. J. Chou, J. Sole, A. Nichols, J. S. Ross, L. A. Tartaglia, and H. Chen "Chronic inflammation in fat plays a crucial role in the development of obesityrelated insulin resistance", J. Clin. Invest., Vol. 112, pp. 1821-1830, 2003. https://doi.org/10.1172/JCI200319451
  13. B. A. Zabel, M. Kwitniewski, M. Banas, K. Zabieglo, K. Murzyn, and J. Cichy, "Chemerin regulation and role in host defense", Am. J. Clin. Exp. Immunol., Vol. 3, pp. 1-19, 2014.
  14. H. Sell, J. Laurencikiene, A. Taube, K. Eckardt, A. Cramer, A. Horrighs, P. Arner, and J. Eckel, "Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells", Diabetes, Vol. 58, pp. 2731-2740, 2009. https://doi.org/10.2337/db09-0277
  15. S. F. Altschul, W. Gish, W. Miller, E. W. Myers, and D. J. Lipman, "Basic local alignment search tool", J. Mol. Biol., Vol. 215, pp. 403-410, 1990. https://doi.org/10.1016/S0022-2836(05)80360-2
  16. H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, and P. E. Bourne, "The protein data bank", Nucleic Acids Res., Vol. 28, pp. 235-242, 2000. https://doi.org/10.1093/nar/28.1.235
  17. J. D. Thompson, D. G. Higgins, and T. J. Gibson, "CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice", Nucleic Acids Res., Vol. 22, pp. 4673-4680, 1994. https://doi.org/10.1093/nar/22.22.4673
  18. B. K. Kuntal, P. Aparoy, and P. Reddanna, "EasyModeller: A graphical interface to MODELLER", BMC Research Notes, Vol. 3, pp. 226, 2010. https://doi.org/10.1186/1756-0500-3-226
  19. N. Eswar, M. A. Marti-Renom, B. Webb, M. S. Madhusudhan, D. Eramian, M. Shen, U. Pieper, and A. Sali, "Comparative protein structure modeling with MODELLER", Current Protocols in Bioinformatics, 2006.
  20. Y. Zhang, "I-TASSER server for protein 3D structure prediction", BMC Bioinformatics, Vol. 9, pp. 40, 2008. https://doi.org/10.1186/1471-2105-9-40
  21. S. C. Lovell, I. W. Davis, W. B. Arendall III, P. I. W. Bakker, J. M. Word, M. G. Prisant, J. S. Rich ardson, and D. C. Richardson, "Structure validation by C${\alpha}$ geometry: $\Phi$, $\Psi$ and C${\beta}$ deviation", Proteins: Structure, Function & Genetics, Vol. 50, pp. 437450, 2002.
  22. C. Colovos and T. O. Yeates, "Verification of protein structures: patterns of non-bonded atomic interactions", Protein Sci., Vol. 2, pp. 1511-1519, 1993. https://doi.org/10.1002/pro.5560020916

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