Visual exploratory assessment of class C GPCR extracellular domains discrimination capabilities

Abstract

G protein-coupled receptors (GPCRs) are integral membrane-bound proteins. They are divided in five main classes with Class C members receiving recently special attention because of their involvement in many neurologic diseases. These receptors are composed of the seven-helix transmembrane domain (typical of all GPCRs) and a large extracellular domain where the endogenous ligand binds. In the present absence of crystal structures for complete Class C receptors, their primary sequences can provide limited but useful information that can be used for subtype discrimination in first instance. In this paper, we show that the extracellular part of these sequences provides as effective a discrimination as the complete sequence. With that purpose, we describe a process of exploratory sequence visualization using different data transformations and manifold learning techniques for dimensionality reduction. Class discriminability is assessed using an entropy-based measure.