Chapter 7: Biomolecules (Organic Molecules)

7.3. Proteins

Learning Objectives

By the end of this section, you will be able to:

  • Describe the functions proteins perform in the cell and in tissues.
  • Discuss the relationship between amino acids and proteins.
  • Explain the four levels of protein organization.
  • Describe the ways in which protein shape and function are linked.
  • Define and describe protein denaturation and its effect on protein shape.

Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Each cell in a living system may contain thousands of proteins, each with a unique function. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers.

Types and Functions of Proteins

Enzymes, which living cells produce, are catalysts in all biochemical reactions. and are usually complex. Each enzyme is specific for the substrate (a reactant that binds to an enzyme) upon which it acts. The enzyme may help in breakdown, rearrangement, or synthesis reactions. We call enzymes that break down their substrates catabolic enzymes. Those that build more complex molecules from their substrates are anabolic enzymes, and enzymes that affect the rate of reaction are catalytic enzymes. Note that all enzymes increase the reaction rate and, therefore, are organic catalysts. An example of an enzyme is salivary amylase, which hydrolyzes its substrate amylose, a component of starch.

Hormones are chemical-signaling molecules, usually small proteins or steroids, secreted by endocrine cells that act to control or regulate specific physiological processes, including growth, development, metabolism, and reproduction. For example, insulin is a protein hormone that helps regulate the blood glucose level. Figure 7.3.1. lists the primary types and functions of proteins.

 Figure 7.3.1:  Protein Types and Functions
Type Examples Functions
Digestive Enzymes Amylase, lipase, pepsin, trypsin Help in food by catabolizing nutrients into monomeric units
Transport Hemoglobin, albumin Carry substances in the blood or lymph throughout the body
Structural Actin, tubulin, keratin Construct different structures, like the cytoskeleton
Hormones Insulin, thyroxine Coordinate different body systems’ activity
Defense Immunoglobulins Protect the body from foreign pathogens
Contractile Actin, myosin Effect muscle contraction
Storage Legume storage proteins, egg white (albumin) Provide nourishment in early embryo development and the seedling
Proteins have different shapes and molecular weights. Some proteins are globular in shape; whereas, others are fibrous in nature. For example, hemoglobin is a globular protein, but collagen, located in our skin, is a fibrous protein. Protein shape is critical to its function, and many different types of chemical bonds maintain this shape. Changes in temperature, pH, and exposure to chemicals may lead to permanent changes in the protein’s shape, leading to loss of function, or denaturation. Different arrangements of the same 20 types of amino acids comprise all proteins. 

Amino Acids

Amino acids are the monomers of proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (-NH2), a carboxyl group (-COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group (also called the side chain) (Figure 7.3.2.).

The molecular structure of an amino acid is given. An amino acid has an alpha carbon to which an amino group, a carboxyl group, a hydrogen, and a side chain are attached. The side chain varies for different amino acids, and is designated as the R - group.
Figure 7.3.2: Amino acids have a central asymmetric carbon to which an amino group, a carboxyl group, a hydrogen atom, and a side chain (R group) are attached.

The name “amino acid” is used because these acids contain both amino group and carboxyl-acid-group in their basic structure. There 20 amino acids that make up proteins (Figure 7.3.3.). Each amino acid differs in its R groups (the side chain or variant group). Nine of these are essential amino acids (must be in the diet).

The molecular structures of the twenty amino acids commonly found in proteins are given. These are divided into five categories: nonpolar aliphatic, polar uncharged, positively charged, negatively charged, and aromatic. Nonpolar aliphatic amino acids include glycine, alanine, valine, leucine, methionine, isoleucine, and proline. Polar uncharged amino acids include serine, threonine, cysteine, asparagine, and glutamine. Positively charged amino acids include lysine, arginine, and histidine. Negatively charged amino acids include aspartate and glutamate. Aromatic amino acids include phenylalanine, tyrosine, and tryptophan. For example, in the amino acid glycine, the R group is a single hydrogen; but in alanine the R group is upper C upper H subscript 3 baseline.
Figure 7.3.3: The 20 amino acids. The different amino acids vary by their R group (the variable portion). The R group that determines its chemical that classification as nonpolar, polar, or ionic.

The sequence and the number of amino acids ultimately determine the protein’s shape, size, and function. A covalent bond called the peptide bond, unites amino acid by the dehydration synthesis reaction. To form the peptide bond, amino acid’s carboxyl function group and the incoming amino acid’s amino functional group combine, releasing a water molecule. (Figure 7.3.4.).

The formation of a peptide bond between two amino acids is shown. When the peptide bond forms, the carbon from the carbonyl group becomes attached to the nitrogen from the amino group. The upper O upper H from the carboxyl group and an upper H from the amino group form a molecule of water.
Figure 7.3.4: Peptide bond formation is a dehydration synthesis reaction. The carboxyl group of one amino acid is linked to the incoming amino acid’s amino group. In the process, it releases a water molecule.
The products that such linkages form are peptides. As more amino acids join to this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end the N terminal, or the amino terminal, and the other end has a free carboxyl group, also the C or carboxyl terminal.

Protein structure

As discussed earlier, a protein’s shape is critical to its function. For example, an enzyme can bind to a specific substrate at an active site. If this active site is altered because of local changes or changes in overall protein structure, the enzyme may be unable to bind to the substrate. To understand how the protein gets its final shape or conformation, we need to understand the four levels of protein structure: primary, secondary, tertiary, and quaternary.

Primary (1o) Structure

Primary structure is the linear polymer chain of amino acids (think of railroad cars attached together). When proteins are first synthesized they are in their primary structure. Figure 7.3.5. illustrates a protein with two peptide chains, the hormone insulin. The three-letter abbreviations (Gly, Ile, etc.) are the symbols for the amino acid names. Shape determines function. Any change in the protein’s normal shape destroys its function.
The amino acid sequences for the A chain and B chain of bovine insulin are shown. The A chain is 21 amino acids in length, and the B chain is 30 amino acids in length. One disulfide, or S S bond, connects two cysteine residues in the A chain. Two other disulfide linkages connect the A chain to the B chain.
Figure 7.3.5: The protein hormone insulin (bovine). In each chain, amino acid names are symbolized by three-letter abbreviations (first letter capitalized). The amino acid cysteine (Cys) has a sulfhydryl (SH) side chain and forms disulfide bonds connecting the two chains A and B. A third disulfide bond maintains the shape of the A chain.

Secondary (2o) Structure

The local folding of the polypeptide in some regions gives rise to the secondary structure of the protein. The most common are the α-helix and β-pleated sheet structures (Figure 7.3.6.). Both structures are held in shape by hydrogen bonds. The hydrogen bonds form between the oxygen atom in the carbonyl group in one amino acid and another amino acid that is four amino acids farther along the chain.

The illustration shows an alpha helix protein structure, which coils like a spring, and a beta-pleated sheet structure, which forms flat sheets stacked together. In an alpha-helix, hydrogen bonding occurs between the carbonyl group of one amino acid and the amino group of the amino acid that occurs four residues later. In a beta-pleated sheet, hydrogen bonding occurs between two different lengths of peptide that are antiparallel to one another.
Figure 7.3.6: The α-helix and β-pleated sheet are secondary protein structures. Certain amino acids have a propensity to form an α-helix while others favor β-pleated sheet formation. Black = carbon, White = hydrogen, Blue = nitrogen, and Red = oxygen. Credit: Rao, A., Ryan, K. Fletcher, S. and Tag, A. Department of Biology, Texas A&M University.

Tertiary (3o) Structure

Proteins in tertiary structure are also called globular proteins (the globins) because of their unique spherical three-dimensional shape (Figure 7.3.7.). This structure is in part due to chemical interactions at work on the polypeptide chain. Primarily, R group interactions create the protein’s complex three-dimensional tertiary structure. For example, R groups with unlike charges are attracted to each other (ionic bonds) and bring the chain close in a loop. Like charges repel each other preventing loop formation. When protein folding takes place, the nonpolar hydrophobic amino acids R groups lie in the protein’s interior; whereas, the hydrophilic R groups lie on the outside. Interaction between cysteine (Cys) side chains forms the disulfide linkages in the presence of oxygen, the only covalent bond that forms during protein folding.

All of these interactions, weak and strong, determine the protein’s final three-dimensional shape. When a protein loses its three-dimensional shape, it loses is function.

This illustration shows a polypeptide backbone folded into a three-dimensional structure. Chemical interactions between amino acid side chains maintain its shape. These include an ionic bond between an amino group and a carboxyl group, hydrophobic interactions between two hydrophobic side chains, a hydrogen bond between a hydroxyl group and a carbonyl group, and a disulfide linkage.
Figure 7.3.7: Tertiary structure of protein. Interactions include hydrophobic interactions, ionic bonding, hydrogen bonding, and disulfide linkages.

Quaternary (4o) Structure

In nature, some proteins form from several polypeptides, or subunits, and the interaction of these subunits forms the quaternary structure. Weak interactions between the subunits help to stabilize the overall structure. Quaternary structure is most common illustrated by the protein molecule hemoglobin, the oxygen-carrier in red blood cells (Figure 7.3.8.)

A complex spherical shape made of ribbons that are coiled and wound around each other. There are 4 large regions (each made from a separate ribbon) – alpha 1, alpha 2, beta 1, beta 2. There are also red spheres attached to each ribbon; these are labeled heme group.
Figure 7.3.8: A hemoglobin molecule shown as a ribbon structure. It has four protein subunits: two alpha, α, subunits (141 amino acids each) and two beta, β, subunits (146 amino acids each)  that come together.  Each subunit binds a heme group, which is the site of oxygen binding.

The four levels of protein organized are summarized below (Figure 7.3.9)

Shown are the four levels of protein structure. The primary structure is the amino acid sequence. Secondary structure is a regular folding pattern due to hydrogen bonding. Tertiary structure is the three-dimensional folding pattern of the protein due to interactions between amino acid side chains. Quaternary structure is the interaction of two or more polypeptide chains.
Figure 7.3.9: The four levels of protein structure (Credit: Rao, A. Ryan, K. and Tag, A. Department of Biology, Texas A&M University)

Denaturation and Protein Folding

Each protein has its own unique sequence and shape that chemical interactions hold together. If the protein is subject to changes in temperature, pH, or exposure to chemicals, the protein structure may change. Bonds (hydrogen bonds) holding the protein together become disrupted causing it to lose its higher level organization shape. The molecule unravels in a process called denaturation (Figure 7.3.10.).

Image depicting a protein on the left with secondary and tertiary structure. An arrow representing Heat points to the same protein on the right that has tertiary and secondary structures unfolded and disorganized.
Figure 7.3.10: Denaturation of a protein unravels the polypeptide.

Denaturation may be irreversible, leading to loss of function. One example of irreversible protein denaturation is frying an egg. The albumin protein in the liquid egg white denatures when placed in a hot pan. Not all proteins denature at high temperatures. For instance, bacteria that survive in hot springs have proteins that function at temperatures close to boiling. The stomach is also very acidic, has a low pH, and denatures proteins as part of the digestion process; however, the stomach’s digestive enzymes retain their activity under these conditions.

Biological enzymes are particularly vulnerable to denaturation because their globular (tertiary) structure is maintained by relatively weak intramolecular interaction. Slight changes in pH or temperature may result in denaturation. That is why blood pH that is outside the homeostatic range (7.35 – 7.45) or extremely high fevers can be fatal. We have some protection against denaturation, however, in the form of a group of proteins known as molecular chaperones (helpers) that prevent protein denaturation and/or refold proteins that have been subjected abnormal conditions (e.g. temperature increases).

License and attributions:

  • Microbiology, 2016, Parker, N. et al. License: CC BY 4.0. Located at https://openstax.org/books/microbiology/pages/7-2-carbohydrates
  • Organic Chemistry, 2023, McMurry, J. License: CC BY 4.0. Located at https://openstax.org/books/organic-chemistry/pages/26-9-protein-structure

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BIO130: Introduction to Physiology Copyright © 2024 by Dinor Dhanabala; Sandra Fraley; and Gordon Lake is licensed under a Creative Commons Attribution 4.0 International License, except where otherwise noted.

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