Abstract
G protein-coupled receptors are eukaryotic cell membrane proteins with a key role as extracellular signal transmitters. While GPCRs embrace a wide and heterogeneous super-family of proteins, our interest in this study is in its Class C, of great relevance to pharmacology. The scarcity of knowledge about their full 3-D crystal structure makes the use of their primary amino acid sequences important for analysis. In this paper, we systematically analyze whether segments of the receptor sequences are able to discriminate between the different class C GPCR subtypes according to their topological location on the extracellular, transmembrane or intracellular domain. For this, we build on previous research that showed that the use of the extracellular N-terminus domain on its own for this classification task did only entail a minor decrease in subtype discrimination when compared to the complete sequence. We use Support Vector Machine-based classification models to assess the subtype discriminating power of the topological segments.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Notes
- 1.
- 2.
References
Santos, R., et al.: A comprehensive map of molecular drug targets. Nature Rev. Drug Discov. 16, 19–34 (2017)
Leach, K., Gregory, K.J.: Molecular insights into allosteric modulation of Class C G protein-coupled receptors. Pharmacol. Res. 116, 105–118 (2017)
Kniazeff, J., et al.: Dimers and beyond: the functional puzzles of class C GPCRs. Pharmacol. Ther. 130, 9–25 (2011)
Cooke, R.M., Brown, A.J., Marshall, F.H., Mason, J.S.: Structures of G protein-coupled receptors reveal new opportunities for drug discovery. Drug Discov. Today 11, 1355–1364 (2015)
Wu, H., et al.: Structure of a class C GPCR metabotropic glutamate receptor 1 bound to an allosteric modulator. Science 344(6179), 58–64 (2014)
Doré, A.S., et al.: Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain. Nature 551, 557–562 (2014)
König, C., Cruz-Barbosa, R., Alquézar, R., Vellido, A.: SVM-based classification of class C GPCRs from alignment-free physicochemical transformations of their sequences. Lecture Notes in Computer Science, vol. 8158, pp. 336–343 (2013)
König, C., Alquézar, R., Vellido, A., Giraldo, J.: Finding class C GPCR subtype-discriminating n-grams through feature selection. J. Integr. Bioinform. 11(3), 254 (2014)
Pin, J.P., Galvez, T., Prezeau, L.: Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol. Ther. 98(3), 325–354 (2003)
König, C., Alquézar, R., Vellido, A., Giraldo, J.: The extracellular N-terminal domain suffices to discriminate class C G protein-coupled receptor subtypes. In: Proceedings of the Joint-Conference on Artificial Neural Networks (IJCNN 2015), pp. 1–7 (2015)
Isberg, V., et al.: GPCRdb: an information system for G protein-coupled receptors. Nucleic Acids Res. 44, 356–364 (2016)
Pin, J.P., Bettler, B.: Organization and functions of mGlu and GABAB receptor complexes. Nature 540, 60–68 (2016)
Vapnik, V.N.: Statistical Learning Theory. Wiley-Interscience, New York (1998)
Breiman, L.: Random forests. Mach. Learn. 45, 5–32 (2001)
John, G., Langley, P.: Estimating continuous distributions in bayesian classifiers. In: Proceedings of the 11th Conference on Uncertainty in Artificial Intelligence, pp. 338–345 (1995)
Chang, C., Lin, C.: LIBSVM: a library for support vector machines. ACM Trans. Intell. Syst. Technol. 2, 27:1–27:27 (2011)
Opiyo, S.O., Moriyama, E.N.: Protein family classification with partial least squares. J. Proteome Res. 6(2), 846–853 (2007)
Liu, B., et al.: Using amino acid physicochemical distance transformation for fast protein remote homology detection. PLoS ONE 7(9), 1–7 (2012)
Cheng, B., et al.: Protein classification based on text document classification techniques. Proteins: Struct. Funct. Bioinf. 58(4), 955–970 (2005)
Bendtsen, J.D., Nielsen, H., von Heijne, G., Brunak, S.: Improved prediction of signal peptides: signalP 3.0. J. Mol. Biol. 340(4), 783–795 (2004)
Acknowledgments
This research was partially funded by the Spanish MINECO TIN2016-79576-R and SAF2014-58396-R project.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this paper
Cite this paper
König, C., Alquézar, R., Vellido, A., Giraldo, J. (2017). Topological Sequence Segments Discriminate Between Class C GPCR Subtypes. In: Fdez-Riverola, F., Mohamad, M., Rocha, M., De Paz, J., Pinto, T. (eds) 11th International Conference on Practical Applications of Computational Biology & Bioinformatics. PACBB 2017. Advances in Intelligent Systems and Computing, vol 616. Springer, Cham. https://doi.org/10.1007/978-3-319-60816-7_20
Download citation
DOI: https://doi.org/10.1007/978-3-319-60816-7_20
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-60815-0
Online ISBN: 978-3-319-60816-7
eBook Packages: EngineeringEngineering (R0)