Signal transduction refers to these cellular processes by which stimuli, either physical or chemical, induce specific cellular responses, through chosen molecular mechanisms. The specificity of a cellular response to a signal depends on the receptor expressed on the target cell.
G-protein coupled receptors (GPCRs) are a very important superfamily of cell membrane receptors in eukaryotic cells. They may interact with both the environment outside and inside the cell and they play a crucial role in receiving stimuli signals from the environment. In response they induce certain cellular responses. GPCRs have a characteristic structure comprised of seven transmembrane-spanning α-helices, an extracellular N terminus, an intracellular C terminus and three interhelical loops on each side of the membrane (1
). Several classification systems have been used for this superfamily categorization. The most frequently system used (2
) classifies GPCRs in six classes, based on their sequence homology and their functional similarity. These are: Class A or 1 Rhodopsin-like, Class B or 2 Secretin receptor family, Class C or three Metabotropic glutamate/pheromone, Class D or four Fungal mating pheromone receptors, Class E or five Cyclic AMP receptors and Class F or six Frizzled/Smoothened like, first presented by (4
). GPCRs that are not yet characterized or classified are called orphan GPCRs. Furthermore, a number of putative classes of some newly discovered GPCRs exist, whose nomenclature has not yet been accepted by the scientific community (5
). Ligands bind to GPCRs on the outside of the cell, activating the GPCRs by causing a conformational change, and allowing them to bind to G-proteins (7
G-proteins form heterotrimers composed of Gα, Gβ and Gγ subunits, which possess a binding site for a GTP or a GDP molecule. They are characterized by their α-subunits, which are further grouped into the Gαs, Gαi/o, Gαq and Gα12 families (8
). The stimulation of GPCRs leads to the activation of G-proteins, which dissociate into their Gα and Gβγ subunits. The subunits then activate several effector molecules that lead to many kinds of cellular and physiological responses (1
). Effectors form a diverse group of proteins through their interaction with G-proteins that act either as secondary messengers, or lead directly to a cellular and physiological response. Many proteins such as tubulins, adenylate cyclases, ion channels and others act as effectors (5
). GPCRs, G-proteins, effectors and their interactions compose one of the main mechanisms for signal transduction and activation or deactivation of pathways within the cell. A large part of efforts towards drug development today is focused on finding chemicals that affect the ability of ligands to bind to GPCRs (9
) either to inhibit or accelerate certain cellular processes. GPCRs play a crucial role in a wide range of human diseases.
Human-gpDB was developed as a tool for integrating together human GPCRs, G-proteins and effectors. It does not only present how they interact with each other but it also reveals information about the pathways they are involved in. Human-gpDB was built as a useful tool for drug research and as a platform that reveals new patterns for therapeutic paths.