The future of medicine is personalized methods of selective exposure to individual cell systems that are responsible for the development and course of a particular disease. The main class of therapeutic targets in this case are the membrane proteins of the cell as the structure responsible for the direct transmission of signals to the cell. Already today, almost half of the drugs affect cell membranes, and then there will only be more. This article is devoted to acquaintance with the biological role of membrane proteins.
The structure and functions of the cell membrane
From the school course, many remember the structure of the structural unit of the body - cells. A special place in the structure of a living cell is played by the plasmalemma (membrane), which separates the intracellular space from its environment. Thus, its main function is to create a barrier between cellular contents and extracellular space. But this is not the only function of the plasmolemma. Among other functions of the membrane, primarily associated with membrane proteins, there are:
- Protective (binding of antigens and prevention of their penetration into the cell).
- Transport (providing metabolism between the cell and the environment).
- Signaling (built-in receptor protein complexes provide cell irritability and its response to various external influences).
- Energy - the conversion of various forms of energy: mechanical (flagella and cilia), electrical (nerve impulse) and chemical (synthesis of adenosine triphosphoric acid molecules).
- Contact (providing communication between cells using desmosomes and plasmodesmata, as well as folds and outgrowths of plasmolemma).
Membrane structure
The cell membrane is a double layer of lipids. The bilayer is formed due to the presence in the molecule of lipids of two parts with different properties - a hydrophilic and hydrophobic site. The outer layer of membranes is formed by polar “heads” with hydrophilic properties, and the hydrophobic “tails” of the lipids are turned into the bilayer. In addition to lipids, proteins enter the membrane structure. In 1972, American microbiologists S.D. Singer (S. Jonathan Singer) and G.L. Nicholson (Garth L. Nicolson) proposed a liquid-mosaic model of the membrane structure, according to which, membrane proteins "float" in the lipid bilayer. This model was supplemented by the German biologist Kai Zimons (1997) in terms of the formation of certain, denser regions with associated proteins (lipid rafts) that freely drift into the bilayer of the membrane.
The spatial structure of membrane proteins
In different cells, the ratio of lipids to proteins is different (from 25 to 75% of the proteins in terms of dry weight), and they are located unevenly. By location, proteins can be:
- Integral (transmembrane) - embedded in the membrane. At the same time, they penetrate the membrane, sometimes repeatedly. Their extracellular regions often carry oligosaccharide chains, forming glycoprotein clusters.
- Peripheral - located mainly on the inner side of the membranes. Communication with the lipids of the membrane is provided by hydrogen reversible bonds.
- Anchored — predominantly located on the outside of the cell, and the “anchor” that holds them to the surface is a lipid molecule immersed in a bilayer.
Functionality and Responsibilities
The biological role of membrane proteins is diverse and depends on their structure and location. Among them, receptor proteins, channel (ionic and porins), transporters, motors, and structural protein clusters are distinguished. All types of membrane protein receptors in response to any effect change their spatial structure and form a cell response. For example, the insulin receptor regulates the flow of glucose into the cell, and rhodopsin in sensitive cells of the organ of vision triggers a cascade of reactions that lead to the emergence of a nerve impulse. The role of membrane protein channels is to transport ions and maintain the difference in their concentrations (gradient) between the internal and external environment. For example, sodium-potassium pumps provide the exchange of the corresponding ions and the active transport of substances. Porins - through proteins - are involved in the transfer of water molecules, transporters - in the transfer of certain substances against the concentration gradient. In bacteria and protozoa, the movement of flagella is ensured by molecular protein motors. Structural membrane proteins support the membrane itself and provide the interaction of other plasmolemma proteins.
Proteins for the membrane, membrane for proteins
A membrane is a dynamic and very active medium, and not an inert matrix for the proteins that are located and work in it. It significantly affects the work of membrane proteins, and lipid rafts, moving, form new associative bonds of protein molecules. Many proteins simply do not work without partners, and their intermolecular interaction is ensured by the nature of the lipid layer of the membranes, the structural organization of which, in turn, depends on structural proteins. Violations in this subtle mechanism of interaction and interdependence lead to impaired membrane protein functions and a number of diseases, such as diabetes and malignant tumors.
Structural organization
Modern ideas about the structure and structure of membrane proteins are based on the fact that in the peripheral membrane part most of them rarely consists of one, more often of several associated oligomerizing alpha-helices. Moreover, just such a structure is the key to fulfilling the function. However, it is the classification of proteins by type of structure that can bring many more surprises. Of the more than one hundred proteins described, the most studied type of membrane protein oligomerization is glycophorin A (erythrocyte protein). For transmembrane proteins, the situation looks more complicated - only one protein is described (the photosynthetic reaction center of bacteria - bacteriorhodopsin). Given the high molecular weight of membrane proteins (10-240 thousand daltons), molecular biologists have a wide field for research.
Cell signaling systems
Among all plasmolemma proteins, a special place belongs to receptor proteins. It is they who regulate which signals enter the cell and which do not. In all multicellular and some bacteria, information is transmitted through special molecules (signaling). Among these signaling agents, hormones (proteins specially secreted by cells), non-protein formations and individual ions are secreted. The latter can be released when neighboring cells are damaged and trigger a cascade of reactions in the form of pain, the main protective mechanism of the body.
Targets for pharmacology
It is membrane proteins that are the main targets of the use of pharmacology, since they are precisely the points through which most signals pass. "Target" a drug, ensure its high selectivity - this is the main task when creating a pharmacological agent. The selective effect only on a specific type or even a subtype of the receptor is the effect on only one type of body cells. Such selective exposure can, for example, distinguish tumor cells from normal cells.
Medicines of the future
The properties and characteristics of membrane proteins are already used in the creation of new generation drugs. These technologies are based on the creation of modular pharmacological structures from several molecules or nanoparticles “crosslinked” with each other. The “targeting” part recognizes certain receptor proteins on the cell membrane (for example, those associated with the development of cancer). To this part is added a membrane-destroying agent or a blocker of processes for producing proteins in the cell. Developing apoptosis (a program of own death) or another mechanism of the cascade of intracellular transformations leads to the desired result of exposure to a pharmacological agent. As a result, we have a cure with a minimum of side effects. The first such anti-cancer drugs are already undergoing clinical trials and will soon become the key to highly effective therapy.
Structural genomics
Modern science of protein molecules is increasingly moving to information technology. An extensive way of research is to study and describe everything that is possible, save data in computer databases and then look for ways to apply this knowledge - this is the goal of modern molecular biologists. Only fifteen years ago, the global project “human genome” was launched, and we already have a sequenced map of human genes. The second project, the purpose of which is to determine the spatial structure of all the “key proteins”, structural genomics, is far from complete. The spatial structure has so far been determined for only 60 thousand of more than five million human proteins. And while scientists have only grown luminous piglets and cold-resistant tomatoes with the salmon gene, the technology of structural genomics remains the stage of scientific knowledge, the practical application of which will not take long.