The tertiary structure of a protein is the way in which a polypeptide chain is folded in three-dimensional space. This conformation arises due to the formation of chemical bonds between amino acid radicals 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 giving proteins functional activity.
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 the covalent disulfide) are very weak, but due to the quantity they stabilize the spatial shape of the molecule.
In fact, the third level of folding of polypeptide chains is a combination of various elements of the secondary structure (α-helices; β-pleated layers andloops), which are oriented in space due to chemical interactions between side amino acid radicals. To schematically indicate the tertiary structure of a protein, α-helices are indicated by cylinders or spiral 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, so two molecules with the same primary structure under equal conditions will correspond to the same variant of spatial packing. This conformation ensures the functional activity of the protein and is called native.
During the folding of a protein molecule, the components of the active center come closer, 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 multi-subunit proteins form a quaternary structure that characterizes the arrangement of several chains in relation to each other.
Characterization of chemical bonds in the tertiary structure of a protein
To a large extent, the folding of the polypeptide chain is due to the ratio of hydrophilic and hydrophobic radicals. The former tend to interact with hydrogen (a constituent element of water) and therefore are on the surface, while hydrophobic regions, on the contrary, rush to the center of the molecule. This conformation is energetically the most favorable. ATthe result is a globule with a hydrophobic core.
Hydrophilic radicals, which nevertheless fall into the center of the molecule, interact with each other to form 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, CONH2) 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. Typically, these groups are spaced apart in a linear chain and approach each other only during the stacking process. Disulfide bonds are not characteristic of most intracellular proteins.
Conformational lability
Since the bonds that form the tertiary structure of a protein are very weak, the Brownian motion of atoms in an amino acid chain can cause them to break and form 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.
Protein conformation is influenced by its interactions with othersmolecules or changes in the physical and chemical parameters of the medium.
How the tertiary structure of a protein is formed
The process of folding a protein into its native form is called folding. This phenomenon is based on the desire of the molecule to adopt a conformation with a minimum value of free energy.
No protein needs intermediary instructors who will determine the tertiary structure. The laying pattern is initially "recorded" in the sequence of amino acids.
However, under normal conditions, in order for a large protein molecule to adopt a native conformation corresponding to the 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 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, which was shown by in vitro experiments.
Folding factors
Auxiliary proteins involved in folding are divided into two groups:
- foldases - have catalytic activity, are required in an amount significantly inferior to the concentration of the substrate (like other enzymes);
- chaperones - proteins with a variety of mechanisms of action, needed in a concentration comparable to the amount of folded substrate.
Both types of factors participate in folding, but are not included infinal 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, since covalent interactions are very strong, and in the event of erroneous connections, the protein would not be able to rearrange itself and take on a native conformation.
- Peptidyl-prolyl-cis-trans-isomerase - provides a change in the configuration of radicals located on the sides of proline, which changes the nature of the bend of the polypeptide chain in this area.
Thus, foldases play a corrective role in the formation of the tertiary conformation of the 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 protein families: hsp60, hsp70 and hsp90. These proteins perform many functions, including:
- Protection of proteins from denaturation;
- exclusion of the interaction of newly synthesized proteins with each other;
- preventing the formation of incorrect weak bonds between radicals and their labialization (correction).
Thus, chaperones contribute to the rapid acquisition of the energetically correct conformation, excluding random enumeration of many options and protecting not yet ripeprotein molecules from unnecessary interaction with each other. In addition, chaperones provide:
- some types of protein transport;
- refolding control (restoration of the tertiary structure after its loss);
- maintaining an unfinished folding state (for some proteins).
In the latter case, the chaperone molecule remains bound to the protein at the end of the folding process.
Denaturation
Violation of the tertiary structure of a protein under the influence of any factors is called denaturation. The loss of the native conformation occurs when a large number of weak bonds that stabilize the molecule are broken. In this case, the protein loses its specific function, but retains its primary structure (peptide bonds are not destroyed during denaturation).
During denaturation, a spatial increase in the protein molecule occurs, and hydrophobic areas again come to the surface. The polypeptide chain acquires the conformation of a random coil, the shape of which depends on which bonds of the protein's tertiary structure have been broken. In this form, the molecule is more susceptible to the effects of proteolytic enzymes.
Factors violating the tertiary structure
There are a number of physical and chemical influences that can cause denaturation. These include:
- temperature above 50 degrees;
- radiation;
- changing the pH of the medium;
- heavy metal s alts;
- some organic compounds;
- detergents.
After the termination of the denaturing effect, the protein can restore the tertiary structure. This process is called renaturation or refolding. Under in vitro conditions, this is possible only for small proteins. In a living cell, refolding is provided by chaperones.
