The term G proteins refers to an inhomogeneous group of proteins that can bind the nucleotides guanosine diphosphate (GDP) and guanosine triphosphate (GTP). They perform a critical function in the transduction and “translation” of extracellular signals into and within the cell. Membrane-bound, heterotrimeric G proteins are the mediators between the extracellular and intracellular space, and so-called small G proteins, which are located in the cytosol of the cells, ensure the transmission of signals within the cell.
What is a G protein?
G proteins, also known as GTPases, represent an inhomogeneous group of proteins that play a critical role in the transduction 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 major 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 act as second messengers for signal transduction within the cell. The membrane-bound G proteins are composed of the subunits alfa, beta and gamma. In the inactive state, GDP is bound to the alfa subunit. An extracellular stimulus (signal) initiates a process in which the GDP is replaced by GTP and, simultaneously, dissociation occurs between the alfa subunit and the beta gamma subunit. The two beta and gamma subunits remain together as the active functional unit in subsequent processes as the beta-gamma subunit. Thus, replacement GDP by GTP corresponds to switching from the inactive “OFF position” to the activated “ON position.”
Function, action, and roles
Human cells, like animal cells, are protected by a cell membrane that is not readily permeable to large molecules or pathogenic germs. On the one hand, the cell membrane provides protection for the interior cytosol and nucleus; on the other hand, this can be a problem for necessary communication and information exchange between cells, within a cell, and between extracellular and intracellular space. The main function of membrane heterotrimeric G proteins, of which about 21 different alpha subunits are known, is signal transduction from the extracellular space to the cell interior. Signal transduction is essential for the transmission of signals and the translation of specific “instructions” into cellular metabolic processes. It is a matter of receiving important messages that are transmitted to the cell from the outside via messenger substances, hormones or neurotransmitters, translating them as “work instructions” for the cell and delivering them inside the cell to second messengers that ensure further transport within the cytosol. Also, the process of transduction plays an important role in the transmission of certain sensitive stimuli such as sight, hearing, taste and smell. Signal transduction is equally important for the functioning of certain regulatory circuits through which body temperature, blood pressure, heart function and many other unconscious parameters are controlled. Put simply, the heterotrimeric G proteins anchored in the cell membrane embody the active clearing site for signaling substances, which are delivered in a transformed form to the small G proteins inside the cell acting as second messengers. The small G proteins, of which more than 100 different forms are known, perform 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 cytoplasm, and the exchange of substances with lysosomes and cell proliferation.
Formation, occurrence, properties, and optimal values
Basic building blocks of G proteins, as with all other proteins, are formed by the so-called proteinogenic amino acids, of which 23 are known to date. While cellular metabolism is capable of synthesizing most amino acids itself, the few amino acids designated as essential must be ingested with food. The assembly of proteins takes place 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 definition, are composed of less than 100 amino acids. The synthesis of G-proteins takes place in each individual cell in complex processes on the basis of the gene segments 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 regulatory processes of each individual cell, and because the ratio between activated and inactivated states is very dynamic, a snapshot of their concentration or activity in the cells is not possible and would not be meaningful. Whether the totality of G proteins in the network are performing “normal” work can only be estimated indirectly by health status.
Diseases and disorders
Proteins that are a functional or activating part of an enzyme, hormone, or other functional entity are at risk of loss of function due to a defect in their amino acid sequence, causing the enzyme or hormone to lose some of its action. In most cases of a “protein defect”, there is a corresponding gene defect. Mutation of a gene segment leads to an incorrect specification of the amino acid sequence and thus to the faulty construction of the corresponding protein. The G proteins are not spared from such genetically determined errors in the building plan. However, functional losses of the G proteins also occur if the error is located in the G protein-coupled receptors. In both cases, the reduced ability to transduce signals triggers or contributes to a particular disease. Diseases associated with impaired G protein function include pseudohypoparathyroidism, acromegaly, hyperfunctional thyroid adenoma, ovarian tumors, and several others.
