A tertiary structure of a protein is a method of folding a polypeptide chain in three-dimensional space. This conformation arises due to the formation of chemical bonds between amino acid radicals that are remote from each other. This process is carried out with the participation of the molecular mechanisms of the cell and plays a huge role in imparting functional activity to proteins.
Features of the tertiary structure
The following types of chemical interactions are characteristic of the tertiary structure of proteins:
- ionic;
- hydrogen;
- hydrophobic;
- van der Waals;
- disulfide.
All these bonds (except for covalent disulfide) are very weak, but due to the amount they stabilize the spatial form of the molecule.
In fact, the third level of folding of the polypeptide chains is a combination of various elements of the secondary structure (α-helices; β-folded layers and loops), which are oriented in space due to chemical interactions between lateral amino acid radicals. For a schematic designation of the tertiary structure of a protein, α-helices are indicated by cylinders or spirally twisted lines, folded layers - by arrows, and loops - by simple lines.
The nature of the tertiary conformation is determined by the sequence of amino acids in the chain, therefore, two molecules with the same primary structure under equal conditions will correspond to the same spatial arrangement. This conformation provides the functional activity of the protein and is called native.
In the process of laying the protein molecule, the components of the active center approach, which in the primary structure can be significantly removed from each other.
For single-stranded proteins, the tertiary structure is the final functional form. Complex multisubunit proteins form a quaternary structure, which characterizes the location of several chains in relation to each other.
Characterization of chemical bonds in the tertiary structure of the protein
To a large extent, folding of the polypeptide chain is due to the ratio of hydrophilic and hydrophobic radicals. The former tend to interact with hydrogen (an integral element of water) and therefore are on the surface, and hydrophobic regions, on the contrary, rush to the center of the molecule. Such a conformation is energetically most beneficial. As a result, a globule with a hydrophobic core is formed.
Hydrophilic radicals, which nevertheless fall into the center of the molecule, interact with each other with the formation of ionic or hydrogen bonds. Ionic bonds can occur between oppositely charged amino acid radicals, which are:
- cationic groups of arginine, lysine or histidine (have a positive charge);
- carboxyl groups of glutamic and aspartic acid radicals (have a negative charge).
Hydrogen bonds are formed by the interaction of uncharged (OH, SH, CONH 2 ) and charged hydrophilic groups. Covalent bonds (the strongest in the tertiary conformation) arise between the SH groups of cysteine residues, forming the so-called disulfide bridges. Usually these groups are removed from each other in a linear chain and come together only during installation. Disulfide bonds are not characteristic of most intracellular proteins.
Conformational lability
Since the bonds that form the tertiary structure of the protein are very weak, the Brownian motion of atoms in the amino acid chain can lead to their breaking and formation in new places. This leads to a slight change in the spatial shape of individual sections of the molecule, but does not violate the native conformation of the protein. This phenomenon is called conformational lability. The latter plays a huge role in the physiology of cellular processes.
The conformation of a protein is affected by its interactions with other molecules or changes in the physicochemical parameters of the medium.
How is the tertiary structure of the protein formed?
The process of laying protein in its native form is called folding. The basis of this phenomenon is the desire of the molecule to accept a conformation with a minimum value of free energy.
No protein needs intermediary instructors who will determine the tertiary structure. The stacking scheme was originally "recorded" in the amino acid sequence.
However, under ordinary conditions, for a large protein molecule to accept the native conformation according to its primary structure, it would take more than a trillion years. Nevertheless, in a living cell, this process lasts only a few tens of minutes. Such a significant reduction in time is provided by the participation in the folding of specialized auxiliary proteins - foldases and chaperones.
The folding of small protein molecules (up to 100 amino acids in a chain) occurs quite quickly and without the participation of intermediaries, as shown by in vitro experiments.
Folding factors
Auxiliary proteins participating in the folding are divided into two groups:
- foldases - have catalytic activity, are required in an amount significantly lower than the concentration of the substrate (like other enzymes);
- chaperones - proteins with various mechanisms of action, are needed in a concentration comparable to the amount of substrate to be rolled up.
Both types of factors participate in folding, but are not part of the final product.
The group of foldases is represented by 2 enzymes:
- Protein disulfide isomerase (PDI) - controls the correct formation of disulfide bonds in proteins with a large number of cysteine residues. This function is very important because covalent interactions are very strong, and in the event of erroneous compounds, the protein could not independently rearrange itself and accept the native conformation.
- Peptidyl-prolyl-cis-trans-isomerase - provides a change in the configuration of radicals located on the sides of the proline, which changes the nature of the bending of the polypeptide chain in this area.
Thus, foldases play a corrective role in the formation of the tertiary conformation of a protein molecule.
Chaperones
Chaperones are otherwise called heat shock or stress proteins . This is due to a significant increase in their secretion during negative effects on the cell (temperature, radiation, heavy metals, etc.).
Chaperones belong to three families of proteins: hsp60, hsp70 and hsp90. These proteins perform many functions, including:
- protein protection against denaturation;
- the exclusion of the interaction of newly synthesized proteins with each other;
- prevention of the formation of irregular weak bonds between radicals and their labilization (correction).
Thus, chaperones contribute to the rapid acquisition of an energetically correct conformation, eliminating the random enumeration of many variants and protecting protein molecules that have not yet matured from unnecessary interaction with each other. In addition, chaperones provide:
- some types of protein transport;
- control of refolding (restoration of the tertiary structure after its loss);
- maintaining the state of unfinished folding (for some proteins).
In the latter case, the chaperone molecule remains bound to the protein upon completion of the folding process.
Denaturation
Violation of the tertiary structure of the protein under the influence of any factors is called denaturation. The loss of native conformation occurs when a large number of weak bonds stabilizing the molecule are destroyed. In this case, the protein loses its specific function, but retains its primary structure (peptide bonds are not destroyed during denaturation).
With denaturation, a spatial increase in the protein molecule occurs, and hydrophobic sites again come to the surface. The polypeptide chain acquires a conformation of a disordered coil, the shape of which depends on what bonds of the tertiary structure of the protein were broken. In this form, the molecule is more susceptible to the effects of proteolytic enzymes.
Tertiary Infringement Factors
There are a number of physico-chemical effects that can cause denaturation. These include:
- temperature above 50 degrees;
- radiation
- change in pH of the medium;
- salts of heavy metals;
- some organic compounds;
- detergents.
After termination of the denaturing effect, the protein can restore the tertiary structure. This process is called renaturation or refolding. In vitro, this is only possible for small proteins. In a living cell, chaperones provide refolding.