The most common type of surface receptor is called a G-protein-coupled receptor. A G-protein-coupled receptor (GPCR) works in conjunction with G protein, which uses guanosine triphosphate (GTP) to activate an effector protein, which is an ion channel or an enzyme. The effector protein is usually an enzyme, which may phosphorylate other proteins, or produce a second messenger to activate a signal transduction pathway. All GPCRs accept an incoming signal from outside the cell and trigger some type of cellular response within the cell. Examples of signaling molecules that use GPCRs include neurotransmitters, epinephrine and other hormones, and the mating factors of yeast cells. GPCRs vary in the binding sites for specific signaling molecules and in the G proteins associated with the cytoplasm side of the receptor. However, the general structure of a GPCR is otherwise consistent across cells and organisms. They have a tertiary structure made from a single polypeptide, or protein chain, which forms characteristic loops between its amino acids. These loops form the binding sites for the signaling molecules outside of the cell and the G proteins inside of the cell's cytoplasm. The G proteins are composed of three subunits, alpha, beta, and gamma. When a ligand binds with the receptor, a guanine diphosphate (GDP) bound to the G proteins is replaced by a GTP, causing the Galpha subunit to detach and stimulate an effector protein. The Galpha and Ggamma subunits also detach as a combined unit and may stimulate a different effector protein. GPCRs are the largest grouping of cell-surface receptors.
GPCR signaling systems are used for many different cellular activities, including embryonic development and taste and smell detection in mammals. Researchers have identified the specific GPCRs that are used for each of the five taste sensations—sweet, sour, bitter, salty, and umami. Sweet, bitter, and umami require genes that produce GPCRs to be determined by the organism. Humans have only one sweet and one umami receptor but about 30 different bitter receptors. For the sense of smell, an odor chemical attaches to a GPCR called an olfactory receptor, located on the cell membranes inside the nose. Once the odor molecules have bound to the GPCR, the cell membranes become permeable to sodium and potassium ions, causing an action potential (change in membrane potential). Mammals can identify thousands of different smells, with some mammals being able to identify far more than others.Some G-protein-coupled receptors activate effector proteins that trigger a signal transduction pathway through the use of a second messenger. A second messenger is a small molecule that carries a message from a membrane receptor into the cytoplasm or may not use the receptor at all. One of the most common examples is adenylyl cyclase, an effector protein that produces the second messenger cyclic AMP (cAMP) during cell signaling. Cyclic AMP (cAMP) is a molecule that regulates many different metabolic functions. It is found in nearly every organism, and it has different effects based on the proteins present in a specific cell. For example, cAMP carries the signal produced by epinephrine from the human kidneys into the interior of a liver or muscle cell, where it binds with an effector protein called protein kinase A (PKA), which initiates a pathway that leads to the breakdown of glucose. The event was originally a mystery because epinephrine cannot easily cross the cell membrane. It was discovered that adenylyl cyclase converts ATP into cAMP in response to epinephrine binding to a G-protein-coupled receptor embedded in the cell membrane.