Proteins in and of themselves are relatively uncomplicated. However, the various substructures and elements that comprise proteins are intricate when considering chemical reactions and connectivity of specific structures and functions of proteins.
Proteins are organic compounds which contain four elements: nitrogen, carbon, hydrogen and oxygen. In order to grasp the entirety of proteins, it is important to understand the various properties of proteins including the basic biological molecule, peptides, polypeptide chains, amino acids, protein structures, and the denaturation processes of proteins.
Proteins are among the most abundant organic molecules in living systems and are vastly diverse in structure and function as compared to other classes of macromolecules. Even one cell contains thousands of proteins, which function in a variety of ways. Proteins are composed of 20 different amino acids, for which genomes dictate the specific amino acids and their sequences.
As a result, variances in protein activities and functions occur due to the complex structural and functional properties of long-evolved proteins. Such properties include:
1. The process of rapid protein folding.
2. Binding sites specific to small groups of molecules.
3. Balanced flexibility in structures and rigidity levels in order to maintain protein functions.
4. Congruent protein surface structures suitable for a protein's environment.
5. Protein vulnerabilities to degradation cause damage, thus rendering protein useless.
Several structural materials are contained within proteins that exist in all living organisms. The many diverse functions relative to these structures are:
– Increases rates of chemical reactions within proteins (e.g. enzymes).
– Strengthens bones, tendons and skin (e.g. collagen).
– Muscle contractions permit movement (e.g. myosin).
• Metabolic regulation
– Joining or taking biomolecules that are needed by the cell.
– Moves oxygen throughout the body (e.g. hemoglobin).
– Protein antibodies serve as protection against foreign pathogens (e.g. immunoglobulin).
Proteins form in different shapes and structures. Some proteins are globular (spherical), compact and water-soluble, while other proteins are fibrous and elongated, physically tough, and water-insoluble. Chemical bonds are responsible for the shapes that proteins maintain.
The 4 Protein Structures
Four different structures of protein serve to influence specific protein activities. Different sequences of amino acids form different shapes and thus, different proteins. All protein activity is based on these four structures:
Primary Structure: The primary structure of a protein is its amino acid sequence. The base (repeat) sequence of the gene codes are comprised of three amino acids (glycine; proline; «x» - any other amino acid). This sequence of amino acids bonded together creates a polypeptide (poly = many) bond, or chain. The primary structure of a protein is linear.
Secondary Structure: The secondary structure takes the chains (primary) and folds, or coils them. These parts attract to one another to form structures that have α(alpha)-helices and β(beta)-pleated sheets. These form as a result of hydrogen bonds between the peptide groups of the main (primary) chain. These secondary-structure proteins contain regions that are cylindrical (α-helices, spiral shape) and/or regions that are planar (β-pleated sheets, ribbon with peaks and valleys). The secondary structure of a structure is three dimensional.
Tertiary Structure: The tertiary structure of a protein is its three-dimensional conformation that is created when the protein folds. Hydrogen bonds stabilize the folding occurrences. Other intramolecular bonds that stabilize the folding processes include hydrophobic interactions; ionic bonds; and disulphide bridges. These bonds are formed between the R groups of amino acids. They contain the nonpolar parts of proteins which result in attractions and repulsions and become coiled up in one area, creating a very complex structure. The tertiary structure is the overall shape of the protein for which most are globular in shape, or fibrous – long and thin.
Quaternary Structure: A quaternary structure is formed when two or more tertiary polypeptide chains form a single or full protein. Certain proteins may have a non-polypeptide structure, thus belonging to a prosthetic group, while other proteins are conjugated. Here unique patterns are formed via hydrogen bonding.
Taking a Closer Look at Peptides
The term protein denotes molecules with >50 combined amino acids. Each protein contains one or more polypeptide chain. The chemical properties and order of the amino acids determines the structure and function of the polypeptide. Each of these polypeptide chains is made up of amino acids, which are joined together in a detailed, deliberate and specific order. Polypeptides have molecular weights that range from several thousand to several million Daltons. Lower molecular weights (<50 amino acids) are categorized as peptides.
The amino acids of a polypeptide are linked together in chains by their neighboring covalent bonds (peptide bonds). In turn, each bond forms in a dehydration synthesis (condensation) reaction. Throughout the protein-synthesis process, the carboxyl group of the amino acid reacts with the amino group of an incoming amino acid, releasing a molecule of water. This process occurs at the end of the growing polypeptide chain, thus resulting in a bond between amino acids, known as a peptide (or polypeptide) chain.
A polypeptide chain has two ends, which are chemically distinct from each other. This is due to the amino acids, which produce directionality of the chain. The two ends of the polypeptide chain are comprised of:
• A free amino group, which is the amino terminus (N-terminus).
• A free carboxyl group (C-terminus).
• Each terminus is located at the opposite end of the other.
In addition to the polypeptide bonds, sulfide bridge formations and Schiff base formations are two other chemical reactions that can take place during cell activities that are «directed» by amino acids, which comprise the basis of all proteins.
Chemical Bonding in Proteins
The amino acids' interactions cause a protein to fold into its mature shape (tertiary). Such folding happens because of the rotation of bonds within the amino acids, as well as bonds joining various amino acids.
Peptide bonds form between the carbonyl carbon and the nitrogen, which is another peptide bond. Nitrogen bonds to carbonyl carbon, then to the peptide linkage, back to the nitrogen, and so on. From the chains, the backbones are interacting. Furthermore, nitrogen is electro-negative such that it consumes electrons from the nitrogen. Here the hydrogen has a partially positive charge.
Conversely, oxygen is electro-negative. Oxygen takes electrons from the carbon which gives oxygen a partially negative charge. Simply put, the hydrogen and the oxygen are attracted to each other, creating a hydrogen bond. From there, these two connected chains form a β-pleated sheet. The backbones then interact with each other and move in the same direction, which is known as a parallel β-pleated sheet.
The β-pleated sheet takes on a certain pattern, moving in the order of nitrogen, α carbon, and then carbonyl carbon. This is on the left side of the protein. On the right side, the pattern moves in the order of carbonyl carbon, α carbon, and then nitrogen. Note that these processes are traveling in opposite directions with the hydrogen bonds between these partially positive ends of the nitrogen-hydrogen bonds remaining at the hydrogen end. The hydrogen bonds and the backbones are still parallel, but again, they are moving in different directions. This is called an anti-parallel β-pleated sheet, which is another form of a secondary structure.
The backbone of the protein can also become a helical structure (also a secondary structure) where the hydrogen bonds form between the different layers of the helix. Remember that oxygen has a partially negative charge, and that hydrogen has a partially positive charge. At any rate, the resulting hydrogen bond gives the protein its helical structure. So these interactions highlight the in-depth and interrelational processes that create the structure, dynamics, and the functions of proteins.
All proteins have the above-mentioned processes in common, but not all proteins possess the more complicated and interactive tertiary and quaternary structures. Several molecular interactions and thermodynamic changes can transpire within these highly complex molecular structures of protein.
Protein denaturation occurs when the three-dimensional structures (in secondary, tertiary, or sometimes quaternary structures) of proteins is altered. Denaturation makes protein non-functional, or at least unable to perform its usual functions. However, the peptide chains are left intact following denaturation, as are the chemical properties of protein. Most usually, the denaturation process is irreversible.
Factors such as heat, cold, or unfavorable pH can cause protein denaturation resulting in damage between the molecular structures of the peptide bonds, thus breaking the otherwise covalent bonds. «Healthy» proteins fold over one another, but denaturation causes them to unravel.
To understand how factors such as high temperature and high or low pH cause denaturation, it is important to remember the fact that hydrogen bonds are crucial in the secondary, tertiary, and sometimes the quaternary structures of protein. A hydrogen bond is a type of peptide bond. Carbon, oxygen, and nitrogen are equally essential in the aforementioned protein structures.
Too much heat, for example, will result in the twisting, bending and rotating of functional molecular groups, and since hydrogen is known to be fragile, it is more vulnerable to ruptures. Temperature increases disrupt the existing hydrogen bonds as well as other non-polar hydrophobic interactions. As the temperature increases, so does the kinetic energy. This causes the molecular components of the protein to vibrate, which leads to the broken bonds. This, in turn, creates a pattern of ruptures or breaks of any nearby hydrogen bonds.
1. Hegyi H, Bork P. On the classification and evolution of protein modules. J Protein Chem. 1997 Jul;16(5):545-51. [PubMed].
2. A. D. Mclachlan. Protein Structure and Function. Annu. Rev. Phys. Chem. 1972.23:165-192.
3. Jay R. Hoffman, Michael J. Falvo. Protein - Which is Best? J Sports Sci Med. 2004 Sep; 3(3): 118-130. [PubMed].
4. Kent SB. Total chemical synthesis of proteins. Chem Soc Rev. 2009 Feb;38(2):338-51. [PubMed].