DOI QR코드

DOI QR Code

Three Dimensional Structure Prediction of Neuromedin U Receptor 1 Using Homology Modelling

  • Received : 2017.02.01
  • Accepted : 2017.03.25
  • Published : 2017.03.30

Abstract

Neuromedin U receptor 1 is a GPCR protein which binds with the neuropeptide, neuromedin. It is involved in the regulation of feeding and energy homeostasis and related with immune mediated inflammatory diseases like asthma. It plays an important role in maintaining the biological clock and in the regulation of smooth muscle contraction in the gastrointestinal and genitourinary tract. Analysing the structural features of the receptor is crucial in studying the pathophysiology of the diseases related to the receptor important. As the three dimensional structure of the protein is not available, in this study, we have performed the homology modelling of the receptor using 5 different templates. The models were subjected to model validation and two models were selected as optimal. These models could be helpful in analysing the structural features of neuromedin U receptor 1 and their role in disorders related to them.

Keywords

References

  1. R. Raddatz, A. E. Wilson, R. Artymyshyn, J. A. Bonini, B. Borowsky, L. W. Boteju, S. Zhou, E. V. Kouranova, R. Nagorny, M. S. Guevarra, M. Dai, G. S. Lerman, P. J. Vaysse, T. A. Branchek, C. Gerald, C. Forray, and N. Adham. "Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system", J. Biol. Chem., Vol, 275, pp. 32452-32459, 2000. https://doi.org/10.1074/jbc.M004613200
  2. A. D. Howard, R. Wang, S. S. Pong, T. N. Mellin, A. Strack, X. M. Guan, Z. Zeng, D. L. Williams Jr, S. D. Feighner, C. N. Nunes, B. Murphy, J. N. Stair, H. Yu, Q. Jiang, M. K. Clements, C. P. Tan, K. K. McKee, D. L. Hreniuk, T. P. McDonald, K. R. Lynch, J. F. Evans, C. P. Austin, C. T. Caskey, L. H. Van der Ploeg, and Q. Liu, "Identification of receptors for neuromedin U and its role in feeding", Nature, Vol. 406, pp. 70-74, 2000. https://doi.org/10.1038/35017610
  3. S. Budhiraja and A. Chugh, "Neuromedin U: physiology, pharmacology and therapeutic potential", Fund. Clin. Pharmacol., Vol. 23, pp. 149-157, 2009. https://doi.org/10.1111/j.1472-8206.2009.00667.x
  4. P. J. Brighton, P. G. Szekeres, and G. B. Willars, "Neuromedin U and its receptors: structure, function, and physiological roles", Pharmacol. Rev., Vol. 56, pp. 231-248. 2004. https://doi.org/10.1124/pr.56.2.3
  5. J. Ballesta, F. Carlei, A. E. Bishop, J. H. Steel, S. J. Gibson, M. Fahey, R. Hennessey, J. Domin, S. R. Bloom, and J. M. Polak, "Occurrence and developmental pattern of neuromedin U-immunoreactive nerves in the gastrointestinal-tract and brain of the rat", Neuroscience, Vol. 25, pp. 797-816, 1988. https://doi.org/10.1016/0306-4522(88)90037-1
  6. C. Austin, M. Oka, K. A. Nandha, S. Legon, N. Khandannia, G. Lo, and S. R. Bloom, "Distribution and developmental pattern of neuromedin-U expression in the rat gastrointestinal-tract", J. mol. Endocrinol., Vol. 12, pp. 257-263, 1994. https://doi.org/10.1677/jme.0.0120257
  7. A. Inui, "Feeding and body-weight regulation by hypothalamic neuropeptides-mediation of the actions of leptin", Trends neurosci., Vol. 22, pp. 6267, 1999.
  8. T. R. Ivanov, C. B. Lawrence, P. J. Stanley, and S. M. Luckman. "Evaluation of neuromedin U actions in energy homeostasis and pituitary function", Endocrinology, Vol. 143, pp. 3813-3821, 2002. https://doi.org/10.1210/en.2002-220121
  9. M. Nakazato, R. Hanada, N. Murakami, Y. Date, M. S. Mondal, M. Kojima, H. Yoshimatsu, K. Kangawa, and S. Matsukura, "Central effects of neuromedin U in the regulation of energy homeostasis", Biochem. Bioph. Res. Co., Vol. 277, pp. 191-194. 2000. https://doi.org/10.1006/bbrc.2000.3669
  10. M. Moriyama, T. Sato, H. Inoue, S. Fukuyama, H. Teranishi, K. Kangawa, T. Kano, A. Yoshimura, and M. Kojima, "The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells", J. Exp. Med., Vol. 202, pp. 217-224, 2005. https://doi.org/10.1084/jem.20050248
  11. N. Minamino, K. Kangawa, and H. Matsuo, "Neuromedin-U-8 and neuromedin-U-25 - novel uterus stimulating and hypertensive peptides identified in porcine spinal-cord", Biochem. Bioph. Res. Co., Vol. 130, pp. 1078-1085, 1985. https://doi.org/10.1016/0006-291X(85)91726-7
  12. N. Minamino, T. Sudoh, K. Kangawa, and H. Matsuo, "Neuromedins: novel smooth-muscle stimulating peptides identified in porcine spinal-cord", Peptides, Vol. 6, pp. 245-248, 1985. https://doi.org/10.1016/0196-9781(85)90381-X
  13. M. S. Mondal, Y. Date, N. Murakami, K. Toshinai, T. Shimbara, K. Kangawa, and M. Nakazato, "Neuromedin U acts in the central nervous system to inhibit gastric acid secretion via CRH system", Am. J. Physiol.-Gastr. L., Vol. 284, pp. G963-G969. 2003. https://doi.org/10.1152/ajpgi.00218.2002
  14. G. C. Baker, J. J. Smith, and D. A. Cowan, "Review and re-analysis of domain-specific 16S primers", J. Microbiol. Meth., Vol. 55, pp. 541-555, 2003. https://doi.org/10.1016/j.mimet.2003.08.009
  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. M. Shalini and T. Madhavan, "Homology Modeling of CCR 4: novel therapeutic target and preferential maker for Th2 cells", J. Chosun Natural Sci., Vol. 7, pp. 234-240, 2014. https://doi.org/10.13160/ricns.2014.7.4.234
  18. B Sathya and T Madhavan, "Homology modeling of cysteinyl leukotriene1 receptor", J. Chosun Natural Sci., Vol. 8, pp. 13-18, 2015. https://doi.org/10.13160/ricns.2015.8.1.13
  19. S. K. Nagarajan and T Madhavan, "3D structure prediction of thromboxane A2 receptor by homology modeling", J. Chosun Natural Sci., Vol. 8, pp. 75-79, 2015. https://doi.org/10.13160/ricns.2015.8.1.75
  20. 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
  21. A. Roy, A. Kucukural, and Y. Zhang, "I-TASSER: a unified platform for automated protein structure and function prediction", Nature Protoc., Vol. 5, pp. 725-738, 2010. https://doi.org/10.1038/nprot.2010.5
  22. N. Eswar, M. A. Marti-Renom, B. Webb, M. S. Madhusudhan, D. Eramian, M. Shen, U. Pieper, and A. Sali, "A comparative protein structure modeling with MODELLER". Current Protocols in Bioinformatics, Vol. 5, pp. 1-5, 2006.
  23. L. J. McGuffin, J. Atkins, B. R. Salehe, A. N. Shuid, and D. B. Roche, "IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences", Nucleic Acids Res., Vol. 43, pp. W169-W173, 2015. https://doi.org/10.1093/nar/gkv236
  24. S. C. Lovell, I. W. Davis, W. B. Arendall III, P. I. W. de Bakker, J. M. Word, M. G. Prisant, J. S. Richardson, and D. C. Richardson, "Structure validation by C${\alpha}$ geometry: $\Phi$, $\Psi$ and C${\beta}$ deviation", Proteins., Vol. 50, pp. 437-450, 2002.
  25. J. U. Bowie, R. Lüthy, and D. Eisenberg, "A method to identify protein sequences that fold into a known three-dimensional structure", Science, Vol. 253, pp. 164-170, 1991. https://doi.org/10.1126/science.1853201
  26. C. Colovos and T. O. Yeates, "Verification of protein structures: patterns of nonbonded atomic interactions", Protein Sci. Vol. 2, pp. 1511-1519, 1993. https://doi.org/10.1002/pro.5560020916
  27. M. Wiederstein and M. J. Sippl, "ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins", Nucleic Acids Res., Vol. 35, pp. W407-W410, 2007. https://doi.org/10.1093/nar/gkm290