Signal Transduction

The G protein coupled receptors (GPCR) illustrate another way to receive and interpret a signal, in which the ligand binds to a single transmembrane protein, causing a conformation change and activating "G proteins" inside the cell. G proteins are so named because they have a binding site for guanine nucleotide, either a diphosphate (GDP) or a triphosphate (GTP). Like ATP, GTP is the high-energy form of the nucleotide, while GDP is the low-energy form.

The GPCR family of proteins has at least 300 members in humans. They are specific receptors for numerous neurotransmitters, hormones, peptides and other substances. A large subgroup of these are odorant receptors directly responsible for our senses of taste and smell.

Surprisingly, a further group of GPCRs is responsible for our sense of vision. Opsin molecules, including rhodopsin, are actually GPCRs. Instead of a ligand binding site, rhodopsin has a molecule of retinal bound in the same relative position. Light alters the conformation of the retinal, and rhodopsin responds to this by altering its protein conformation. This causes G protein activation in a similar manner to the other GPCRs.

Each GPCR is associated with a particular type of G protein inside the cell, and there are dozens of different G proteins known. G proteins are generally inactive in the GDP-bound form. They are activated when GDP departs and is replaced by GTP. GTP is found in excess in cells, and so GDP departure is followed rapidly by GTP binding. This causes a profound conformational change, allowing the G protein to interact with and influence numerous target molecules.

Each GPCR associated G protein consists of three parts, the α, β, and γ subunits. The α subunit binds either GDP or GTP. The β and γ subunits are always found together in a complex called Gβγ. In unstimulated cells the whole three-part complex is found in the plasma membrane, with GDP in the binding site.

Binding of ligand to the GPCR causes a conformational change that is transmitted to the cytoplasmic region of the receptor, which interacts with the G protein to dissociate the GDP. This results in GTP binding, which alters the structure of the α subunit, freeing it from Gβγ. Both parts, the Gα(GTP) and the Gβγ, now diffuse away from the receptor and separately interact with and influence many other molecules in the cell.