Topological Sequence Segments Discriminate Between Class C GPCR Subtypes

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.