G proteins, also referred to as GTPases, represent an inhomogeneous group of proteins that play a crucial role in the transmission of extracellular signals into and within the cell. All G proteins are characterized by their ability to bind the nucleotides GTP and GDP.

They can be divided into the two large groups of membrane-bound heterotrimeric G proteins and the so-called small monomeric G proteins. The monomeric G-proteins are located in the cytosol of the cells and, as second messengers, take over the signal transduction within the cell. The membrane-bound G proteins are composed of the subunits alpha, beta and gamma. In the inactive state, GDP is bound to the alpha subunit.

An extracellular stimulus (signal) initiates a process in which the GDP is replaced by GTP and at the same time a dissociation between the alpha subunit and the beta-gamma subunit occurs. The two beta and gamma subunits remain together as an active functional unit in the subsequent processes as the beta-gamma subunit. Replacing GDP with GTP thus corresponds to switching from the inactive “OFF position” to the activated “ON position”.

Function, effect & tasks

Like animal cells, human cells are protected by a cell membrane that is not easily permeable to large molecules or pathogenic germs. On the one hand, the cell membrane provides protection for the inner cytosol and the cell nucleus , on the other hand, this can pose a problem for the necessary communication and information exchange between cells, within a cell and between the extracellular and intracellular space. 

The main function of the membrane-bound heterotrimeric G proteins, of which about 21 different alpha subunits are known, is signal transduction from the extracellular space to the interior of the cell. Signal transduction is essential for the transmission of signals and the translation of certain “instructions” into cellular metabolic processes . It is about receiving important messages that are brought to the cell from the outside via messenger substances , hormones or neurotransmitters , translating them as “work instructions” for the cell and passing them on to second messengers inside the cell, which ensure further transport within the cytosol .

The process of transduction also plays an important role in the transmission of certain sensory stimuli such as vision , hearing , taste and smell. Signal transduction is just as important for the functioning of certain control circuits that regulate body temperature, blood pressure, heart function and many other unconscious parameters. Put simply, the heterotrimeric G-proteins anchored in the cell membrane embody the active clearing site for signaling substances, which are released in a transformed form to the small G-proteins inside the cell, which act as second messengers.

The small G proteins, of which more than 100 different forms are known, take on a variety of tasks within the cell. For example, they are involved in the regulation of gene expression, the organization of the cytoskeleton, the transport of substances between the nucleus and the cytoplasm, and in the exchange of substances with the lysosomes and in cell proliferation.

Formation, Occurrence, Properties & Optimal Values

As with all other proteins, the basic building blocks of the G proteins are the so-called proteinogenic amino acids , of which 23 are known to date. While the cellular metabolism is able to synthesize most of the amino acids itself, the few amino acids designated as essential must be ingested with food.

The proteins are assembled either from scratch by stringing together amino acids in the genetically predetermined sequence or by assembling already existing fragments of partially disassembled, long-chain proteins. The fragments can also consist of peptides or polypeptides which, according to the definition, are composed of less than 100 amino acids. The G proteins are synthesized in each individual cell in complex processes based on the gene sections previously copied in the mRNA, which specify the amino acid sequence of each individual protein.

Because G proteins in their diversity are involved in practically all control and regulation processes of every single cell and the relationship between the activated and inactivated state is very dynamic, a snapshot of their concentration or activity in the cells is not possible and would also not be meaningful. Whether all of the G proteins in the network perform “normal” work can only be estimated indirectly via the health status.

Diseases & Disorders

In the case of proteins that are a functional or activating part of an enzyme , hormone or other functional unit, there is a risk that they will suffer a loss of function due to an error in their amino acid sequence and the enzyme or hormone will lose part of its effect. In most cases of a “protein error” there is a corresponding genetic defect . 

The mutation of a gene section results in an incorrect specification of the amino acid sequence and thus in the defective construction of the corresponding protein. The G-proteins are not spared from such genetic errors in the construction plan. However, there is also a loss of function of the G proteins if the fault lies with the G protein-coupled receptors.

In both cases, the decreased ability to signal transduce triggers or contributes to a specific disease. Diseases associated with impaired G-protein function include pseudohypoparathyroidism , acromegaly , hyperfunctional thyroid adenoma, ovarian tumors , and a few others.