Proteins are the most diverse biomolecules on Earth, performing many functions required for life. Protein enzymes are biological catalysts, maintaining life by regulating where and when cellular reactions occur. Structural proteins provide internal and external support to protect and maintain cell shape. For example, keratins are an important class of structural proteins found in the hair, skin, nails, and feathers of animals. Motility proteins provide the basis for cellular and whole organism movement, including muscle motor proteins that can move entire animals! Membrane proteins transmit signals during cell-to-cell communication, transport molecules into and out of cells, and protect living organisms by identifying and flagging invaders.
Protein functions are so diverse because of the many unique three-dimensional structures protein polymers form. Despite such variety, proteins also share several specific structural characteristics in their monomers, the amino acids. Structural similarities among amino acids make protein synthesis a uniform and regulated process; however, each amino acid contains a unique structural component as well. Specific differences between each amino acid interact to create unique three-dimensional protein structures. Combined, the similarities and differences between amino acids explain how cells can build a diverse pool of proteins from the same set of building blocks.
In every amino acid, one central carbon atom exists - the alpha-carbon (α-carbon). Of the four atom groups covalently bonded to the α-carbon, three are the same in all amino acids. The α-carbon is always directly bonded to one amino group and to one carboxyl group (carboxylic acid). The name amino acid derives from the presence of these two functional groups (amino + acid). All amino acids share a third common covalent bond to a hydrogen atom, but the fourth atom (or atomic group) bonded to the α-carbon is unique in each amino acid.
The fourth α-carbon bond may link to another single hydrogen atom, as in glycine, or to a group of atoms. Atom groups range in both size and polarity or charge. For example, lysine contains a large and ionic atom group. For simplicity, when a specific amino acid is not identified, biologists use the term “R-group” to refer to the fourth atom or group bonded to the α-carbon. The term “R” signifies the rest of the molecule and is used when discussing general structure and reactivity of amino acids without complicating a structure by inclusion of R-group details.
Protein synthesis involves building a polymer of amino acids with complex three-dimensional structure. Dehydration synthesis forms a peptide bond between amino acids and releases a water molecule. A dipeptide forms when a peptide bond is created between two individual amino acids, connecting the carboxyl-group carbon of one amino acid and the amino-group nitrogen of another amino acid. As additional amino acids are bonded through dehydration synthesis, a short chain (peptide) grows. Polypeptides are formed as peptide chain lengths reach one hundred or more amino acids. Proteins form as amino acids in one or more polypeptides chemically interact to create a complex three-dimensional structure.
Living organisms synthesize almost all proteins using only twenty different amino acids. Polypeptides form a unique three-dimensional structure based on the type and position (sequence) of these amino acids. Within the sequence, amino acid R-groups form chemical interactions that create a specific three-dimensional structure. These R-groups are commonly called “side chains” because they are not involved in the peptide bonds. The R-groups stick out on the side of a polypeptide, freeing them to chemically interact with one another. Side chain interactions form each protein’s specific structure, a structure uniquely capable of performing that protein’s cellular function.
Functional Groups of Proteins
This activity tests your ability to identify functional groups of amino acids in proteins.
Building and Breaking Proteins
This activity tests your ability to identify the reactants and products in protein synthesis and hydrolysis.
Protein Structure and Function
Unlike polysaccharides, polypeptide chains are assembled with a wide variety of amino acids in each polymer. The set of twenty amino acids commonly found in biological proteins is directly responsible for the diversity of protein structures in living cells. Each protein differs in several aspects that determine structure and, therefore, function. A protein may be composed of one or more polypeptide strands. A cell’s genes determine the length of each polypeptide strand, as well as the type and position of each amino acid in the sequence. Together, these factors determine protein structure, which determines the function a protein can perform.
How does protein structure determine function? The three-dimensional shape of each protein is perfectly suited to perform one specific function. For example, aquaporins are channel proteins that form small tunnels through a cell membrane. The internal surface of aquaporin tunnels possesses a specific diameter and polarity. This structure is perfectly designed to transport water molecules but very little else, providing specificity and function. If protein structure changes, so does a protein’s ability to function.
Knowing the importance of protein structure in determining function, how then is protein structure determined? To answer this, we must first ask how only twenty amino acids can create the diversity of proteins we see in living organisms. This diversity is easily explained by the way polypeptides form a sequence. Imagine creating a dipeptide using the twenty common amino acids. Twenty options exist for the first position, and twenty options exist for the second position of this two amino acid peptide. Math calculations tell us that we could synthesize four hundred different dipeptides! For every additional amino acid in a peptide, we multiply this number of options by twenty again. With more than one hundred amino acids in the average sequence, imagine how many different polypeptides may exist in nature!
In addition to increasing variation, each of the twenty common amino acids plays a vital role in the structure and function of proteins in all living organisms. While producers like plants synthesize all twenty common amino acids, consumers, who obtain energy by eating biomolecules, rely on dietary intake to obtain one or more amino acids. Humans synthesize ten of the twenty common amino acids, but the remaining ten must be obtained through diet. Although all amino acids are necessary for human life, the “essential amino acids” are the ones humans cannot synthesize on their own. Eating protein-rich foods provides these essential amino acids to the cells.
Directed by genes, living organisms synthesize polypeptides using amino acids. The unique order of amino acids in a polypeptide is called the primary structure and represents the first level of a protein’s three-dimensional structure (conformation). The primary structure determines every additional level of chemical interactions, directing the formation of a protein’s final conformation.
If structure determines function, how does the primary sequence of amino acids determine a three-dimensional structure? In a process called protein folding, stable chemical interactions form between amino acids in a protein, bending and twisting the polymer into a three-dimensional shape. Protein folding sometimes requires help by molecular chaperone proteins that bind newly forming polypeptides and assist with structure formation.
Protein folding involves three layers of chemical interactions, termed secondary, tertiary, and quaternary structure. Secondary structure is created as hydrogen bonds form between nearby amino acids during protein synthesis. Hydrogen bonds in secondary structure involve the polar amino and carboxyl groups of amino acids, but do not involve R-groups. As the peptide chain continues to grow, interactions between amino acid side chains (R-groups) form the tertiary structure of a polypeptide. Side chains interact with one another by:
- formation of side-chain hydrogen bonds.
- aggregation of hydrophobic side-chains.
- formation of ionic (salt bridge) bonds and covalent (disulfide bridge) bonds.
Although all chemical interactions are important to tertiary structure, proteins fold mainly in response to which side chains are able to form hydrogen bonds with water. Because water molecules are most of a cell’s interior solution, nonpolar side chains are excluded from solution and aggregate as hydrogen bonds form with polar and ionic side chains. These hydrophobic interactions are the strongest determinant of tertiary structure.
In some proteins, folding is complete after formation of tertiary structure. In others, multiple polypeptide chains combine to form a fourth level of structure, quaternary structure. Quaternary structure involves two or more polypeptides folding together through the same types of chemical interactions that formed the tertiary structure. In quaternary structure, the side-chains of different polypeptides form hydrogen bonds, hydrophobic interactions, and chemical bonds with one another. Hemoglobin, the protein that carries oxygen through the bloodstream, consists of four polypeptides.
What if something disrupts protein structure? Extreme heat, changes in pH, and chemical toxins are only a few causes of protein denaturation, the loss of natural protein structure. Some proteins are capable of refolding, but most proteins are unable to recover from significant loss of protein structure. For example, cooking an egg permanently denatures its proteins, changing the appearance and texture of the egg. Living cells expend considerable effort to maintain homeostasis by controlling their internal environment because unexpected changes can destroy a cell’s proteins, killing the cell.
Because protein function relies on precise structure formation, protein folding is a key topic of scientific study. Many biochemists devote their entire careers to finding ways to predict how proteins will fold and how mutations will affect protein structure and function. Mutations that change a protein’s primary sequence can lead to massive changes in protein structure and eliminate or change function, resulting in disease or death. Occasionally, mutations lead to improved or new functions benefittting the organism. Rare beneficial mutations spread through populations through natural selection, leading to evolutionary change.
This animation illustrates the process of denaturation.
This activity tests your ability to match terms related to proteins with their definitions.