The future of medicine is personalized methods of selective influence on 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 cell membrane proteins as structures responsible for providing direct signal transmission to the cell. Already today, almost half of the drugs affect cell membranes, and there will only be more of them in the future. This article is devoted to acquaintance with the biological role of membrane proteins.
Structure and function of the cell membrane
From the school course, many remember the structure of the body's structural unit - the cell. 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 the cellular content and the extracellular space. But this is not the only function of the plasmalemma. Among other membrane functions related tofirst of all with membrane proteins, secrete:
- Protective (binding antigens and preventing their penetration into the cell).
- Transportation (ensuring the exchange of substances between the cell and the environment).
- Signal (built-in receptor protein complexes provide cell irritability and its response to various external influences).
- Energy - transformation of different 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 the plasmolemma).
Structure of membranes
The cell membrane is a double layer of lipids. The bilayer is formed due to the presence in the lipid molecule of two parts with different properties - a hydrophilic and a hydrophobic section. The outer layer of the membranes is formed by polar "heads" with hydrophilic properties, and the hydrophobic "tails" of lipids are turned inside the bilayer. In addition to lipids, the structure of membranes includes proteins. In 1972, American microbiologists S. D. Singer (S. Jonathan Singer) and G. L. Nicholson (Garth L. Nicolson) proposed a fluid-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 Simons (1997) in terms of the formation of certain, denser regions with associated proteins (lipid rafts) that drift freely in the membrane bilayer.
Spatial structure of membrane proteins
In different cells, the ratio of lipids and proteins is different (from 25 to 75% of proteins in terms of dry weight), and they are unevenly located. By location, proteins can be:
- Integral (transmembrane) - built into 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 inside of the membranes. Communication with membrane lipids is provided by reversible hydrogen bonds.
- Anchored - mainly located on the outside of the cell and the "anchor" holding them on the surface is a lipid molecule immersed in the bilayer.
Functionality and responsibilities
The biological role of membrane proteins is diverse and depends on their structure and location. They include receptor proteins, channel proteins (ionic and porins), transporters, motors, and structural protein clusters. All types of membrane protein receptors, in response to any impact, change their spatial structure and form the response of the cell. For example, the insulin receptor regulates the entry of glucose into the cell, and rhodopsin in the sensitive cells of the organ of vision triggers a cascade of reactions that lead to the appearance 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 a concentration gradient. In bacteria and protozoa, the movement of flagella is provided by molecular protein motors. Structural membrane proteins support the membrane itself and ensure the interaction of other plasma membrane proteins.
Membrane proteins, protein membrane
The membrane is a dynamic and very active environment, 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 provided by the nature of the lipid layer of membranes, the structural organization of which, in turn, depends on structural proteins. Disturbances in this delicate mechanism of interaction and interdependence lead to dysfunction of membrane proteins 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 membrane peripheral part, most of them rarely consist of one, more often of several associated oligomerizing alpha-helices. Moreover, it is this structure that is the key to the performance of the function. However, it is the classification of proteins by typestructures can bring many more surprises. Of more than a hundred described proteins, the most studied membrane protein in terms of the type of oligomerization is glycophorin A (erythrocyte protein). For transmembrane proteins, the situation looks more complicated - only one protein has been described (the photosynthetic reaction center of bacteria - bacteriorhodopsin). Given the high molecular weight of membrane proteins (10-240 thousand d altons), molecular biologists have a wide field for research.
Cell signaling systems
Among all the proteins of the plasma membrane, 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 (signal). Among these signaling agents are hormones (proteins specially secreted by cells), non-protein formations, and individual ions. The latter can be released when neighboring cells are damaged and trigger a cascade of reactions in the form of a pain syndrome, the body's main defense mechanism.
Targets for pharmacology
It is membrane proteins that are the main targets of pharmacology, since they are the points through which most signals pass. "Targeting" a drug, ensuring its high selectivity - this is the main task in creating a pharmacological agent. A selective effect on only a specific type or even a subtype of the receptor is an effect on only one type of body cells. Such a selectiveexposure can, for example, distinguish tumor cells from normal ones.
Drugs of the future
Properties and features of membrane proteins are already being used in the creation of new generation drugs. These technologies are based on the creation of modular pharmacological structures from several molecules or nanoparticles “cross-linked” with each other. The “targeting” part recognizes certain receptor proteins on the cell membrane (for example, those associated with the development of oncological diseases). To this part is added a membrane-destroying agent or a blocker in the processes of protein production in the cell. Developing apoptosis (the program of one's 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 drug with a minimum of side effects. The first such cancer-fighting drugs are already in clinical trials and will soon become highly effective therapies.
Structural genomics
Modern science of protein molecules is increasingly moving to information technology. An extensive path of research - to study and describe everything that can be stored in computer databases and then look for ways to apply this knowledge - this is the goal of modern molecular biologists. Just fifteen years ago, the global human genome project started, and we already have a sequenced map of human genes. The second project, which aims to definethe spatial structure of all "key proteins" - structural genomics - is still far from complete. The spatial structure has so far been determined only for 60,000 of more than five million human proteins. And while scientists have grown only luminous piglets and cold-resistant tomatoes with the salmon gene, structural genomics technologies remain a stage of scientific knowledge, the practical application of which will not be long in coming.
