G Proteins

By Jennifer McDowall

To view structure of G proteins

The ability of cells to work together in a co-ordinated fashion is paramount for a multicellular organism to function. The multitude of cell types each have specialised roles to play, yet remain dependent upon the products of other cells for survival. Even the needs of individual cells can change according to their stage of development and environmental conditions. Multicellular organisms had to develop complex systems of control in order to regulate the different processes going on in different cells at different times. For such a system to work, there must be a sophisticated means of communication between cells. GPCRs (G protein-coupled receptor) and their G proteins (guanine nucleotide-binding proteins) form one of the most prevalent signalling systems in mammalian cells, being involved in the control of nearly every aspect of physiology and behaviour. Of the three major groups of receptors – GPCRs, ion channels and tyrosine kinases – GPCRs form the largest family. Their role is to bind specific ligands at the cell surface, such as hormones and neurotransmitters, and to relay the signal across the membrane via heterotrimeric G proteins. The G protein cascade ultimately leads to the regulation of systems as diverse as sensory perception, cell growth, and hormonal regulation.

G proteins, cell regulators

G proteins integrate a multitude of cellular responses, acting as mediators of signalling by many different extracellular compounds, ranging from hormones and neurotransmitters to odorants and photons of light, each one leading to a different biological response. As a result, G proteins must constantly deal with a mass of incoming signals, which must be transmitted and integrated appropriately. To deal with this plethora of information, there needs to be a method of targeting specific effectors to ensure that only the appropriate response is triggered. This is achieved through the modular nature of heterotrimeric G proteins and the diversity of their individual subunits. G proteins are composed of three subunits encoded by distinct genes: a, b, and g. Several isoforms of each subunit exist, which together can make up hundreds of combinations of G proteins. The specific combination of a, b and g subunits affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli. In this way, the diversity of G protein subunits helps to transmit and integrate the many different signals coming into a cell. In humans, genes encoding at least sixteen a subunits, five b subunits and twelve g subunits have been identified, several of which are known to have splice variants, thereby further increasing their variability. G protein classes are defined based on the sequence and function of their a subunits, which fall into four main categories: GaS, GaQ, GaI and Ga12. In many cases, these G proteins can couple to more than one receptor subtype, but with differing affinities.

Next: How G Proteins Work