Peptides and Proteins

Out of all the types of biomolecules, proteins have the most diverse array of functions. They do most of the work within each cell to keep it alive and functioning, transmit signals from one cell to another, help us move, and protect us from villainous intruders, such as bacteria and viruses. Every process required for life is dependent on molecular mechanisms carried out by proteins. There are thousands of different proteins in every living organism, each with unique properties and functions. Like other biomolecules, the properties and functions of proteins depend on their structure. In this topic, we will introduce the structure and function of proteins.

Peptides, polypeptides, proteins

The terms "polypeptide" and "protein" are often used interchangeably, but they do have specific meanings. A polypeptide is a polymer made up of several amino acids joined by peptide bonds.

A protein is one or more polypeptide chains with distinct 3-dimensional structure and a specific function.

Protein functions

Proteins play a wide range of roles in the living organism.

• Antibodies are used by the immune system to identify and neutralize pathogens.
• Enzymes are catalysts that speed up biochemical reactions, such as digestion or synthesis of proteins.
• Messengers, such as hormones and other signaling proteins, transmit signals and coordinate processes between cells, tissues, and organs. Other proteins act as receptors and receive these signals.
• Transport proteins, such as hemoglobin, carry cargo (atoms, molecules, molecular complexes) within cells and throughout a body.
• Storage proteins, such as egg albumin, nourish a developing organism.
• Structural proteins build structures, such as a sperm tail or strand of hair. They can be contractile and allow muscles to move.

Primary structure

There are four distinct levels of protein structure. The simplest level is the primary structure. It is the sequence of amino acid residues. Even the smallest alteration in the primary structure may cause a change in the protein's properties. Though there are about 600 amino acids in hemoglobin, a single amino acid substitution causes sickle cell anemia. Impressive!

Secondary structure

The next level is called the secondary structure. It refers to bends and twists in the polypeptide chain that occur due to interactions between amino acids local to each other. The two main structures are the α-helix and β-sheet. These structures are stabilized through a force called hydrogen bonding. Hydrogen bonds form between the amino hydrogen of one amino acid and the carboxyl oxygen of another amino acid within the polypeptide "backbone." The backbone is the polypeptide chain apart from the R groups, so the R groups are not involved in secondary structures.

An α-helix resembles a curled ribbon or a spiral staircase, where each turn of the helix contains 3.6 amino acid residues. Their R groups extend outwards and are free to interact with each other and chemical groups in the surroundings. A β-pleated sheet is a sheet-like structure where segments of a polypeptide chain line up next to each other. The pleated strands align parallel or antiparallel to each other, and hydrogen bonds form between them. The R groups stick out above and below the plane of the sheet. Certain amino acids are more or less likely to be in α-helices and β-sheets.

Tertiary structure

Tertiary structure is the overall 3-dimensional shape of a single polypeptide chain. During the protein synthesis process, the protein will "fold" or form compact structures out of the collection of α-helices, β-sheets, and other amino acid residues that make up the polypeptide chain. Folding mainly occurs due to non-local interactions between the R groups in the amino acid residues. There are several types of R group interactions that stabilize the tertiary structure.

• Hydrophobic interaction can drive folding. Because hydrophobic amino acids want to avoid contact with water (which makes up most of the protein's environment), they form a hydrophobic core by clustering together and burying their R groups inside the protein. Any hydrophilic amino acids lay on the outside and interact with the surrounding water.
• Ionic bonds are formed between charged amino acids. R groups of amino acids with opposite charges can form a bond, while amino acids with the same charge repel each other. For example, positively-charged histidine can form a bond with negatively-charged glutamate, but it will repel lysine because it also has a positive charge.
• Hydrogen bonds are key to secondary structure formation, but they also participate in protein folding. They connect polar R groups, for example, those of serine and glutamine.
• A salt bridge is a combination of ionic bonding and hydrogen bonding. Salt bridges are common stabilizers in proteins that have energetically unfavorable fold structures. Salt bridges mainly arise from negatively-charged aspartate or glutamate interacting with positively-charged lysine or arginine.
• Disulfide bridges are formed between two sulfur-containing R groups of cysteine residues. These bonds are much stronger than the other interactions listed above. They cross-link regions of a protein, holding them together very firmly.

All of these interactions determine the protein's final 3-dimensional shape or conformation. A protein's function depends on its conformation.

Subtypes of proteins

There are three distinct subtypes of proteins: globular, membrane, and fibrous. They differ in structure, solubility, and function.

Globular proteins have a spherical shape and a hydrophobic core. Hydrophilic groups are exposed on the surface of the sphere, making these proteins soluble in water. These proteins generally perform some sort of biological activity, and one example is hemoglobin.

Membrane proteins are components of cell membranes. Integral proteins are firmly anchored in the membrane, and peripheral proteins are temporarily associated with membranes. Integral proteins can be classified into two groups. Transmembrane proteins span through the membrane, while monotopic proteins are attached to one side of the membrane. Membrane proteins generally serve as receptors to receive signals, transporters to help molecules pass through the membrane, or ligands that help cells interact and recognize each other.

Fibrous proteins are elongated, narrow strands that primarily have a structural role. Keratin, which makes up our hair and nails, and silk, which is used for textiles and other applications, are fibrous proteins. They are made up of amino acid sequences that are repeated multiple times. Fibrous proteins are not soluble in water but dissolve in strong acids and bases.

Denaturation

When bonds that keep a protein in a folded state break, a protein becomes a disordered string of amino acids. This process is called denaturation. Denaturation can happen after treatment with chemical agents, vigorous shaking, or heating. When you fry eggs, colorless albumen turns white because denaturation occurs. On the frying pan, denaturation is irreversible, but in other situations, proteins might be able to regenerate (renaturate) their original structures and functions. Renaturation requires the removal of denaturing agents and restoration of the native conditions of the protein.

Quaternary structure

Many proteins are composed of a single polypeptide chain, but some proteins are actually complexes of several folded polypeptide chains or protein subunits that come together to make a single functional unit. These proteins are said to have quaternary structure. For example, hemoglobin is a protein with a quaternary structure. It is composed of four subunits (two α and two β chains). The overall complex is stabilized by the same types of bonds that form tertiary protein structures. Subunits interact through hydrogen and ionic bonds and can form disulfide bridges.

Conclusion

Proteins are biomolecules that perform a wide range of functions in the living organism. They are polymers composed of amino acids that form complex structures described by the four levels of protein structure: primary, secondary, tertiary, and quaternary. Primary structure refers to the sequence of amino acids. Secondary structure comprises the formation of helices and sheets through hydrogen bonding between amino acids. Tertiary structure is the overall 3D shape of the protein. When two or more protein subunits combine, a quaternary structure is formed. A protein's three-dimensional structure determines its specific function. When a protein loses its native structure and becomes disordered during denaturation, it loses the ability to perform its function.