160 Proteins
Types and Functions of Proteins
Proteins perform many essential physiological functions, including catalyzing biochemical reactions.
Learning Objectives
Differentiate among the types and functions of proteins
Key Takeaways
Key Points
- Proteins are essential for the main physiological processes of life and perform functions in every system of the human body.
- A protein’s shape determines its function.
- Proteins are composed of amino acid subunits that form polypeptide chains.
- Enzymes catalyze biochemical reactions by speeding up chemical reactions, and can either break down their substrate or build larger molecules from their substrate.
- The shape of an enzyme’s active site matches the shape of the substrate.
- Hormones are a type of protein used for cell signaling and communication.
Key Terms
- amino acid: Any of 20 naturally occurring α-amino acids (having the amino, and carboxylic acid groups on the same carbon atom), and a variety of side chains, that combine, via peptide bonds, to form proteins.
- polypeptide: Any polymer of (same or different) amino acids joined via peptide bonds.
- catalyze: To accelerate a process.
Examples
Salivary amylase is an enzyme in the mouth that breaks down starch (a long carbohydrate chain) into amylose (a short chain of glucose molecules). The longer you chew a cracker, the sweeter the cracker will taste because your taste buds are receptive to the glucose molecules exposed by the amylase.
Proteins perform essential functions throughout the systems of the human body. These long chains of amino acids are critically important for:
- catalyzing chemical reactions
- synthesizing and repairing DNA
- transporting materials across the cell
- receiving and sending chemical signals
- responding to stimuli
- providing structural support
Human Hemoglobin: Structure of human hemoglobin. The proteins’ α and β subunits are in red and blue, and the iron-containing heme groups in green. From the protein data base.
Proteins (a polymer) are macromolecules composed of amino acid subunits (the monomers ). These amino acids are covalently attached to one another to form long linear chains called polypeptides, which then fold into a specific three-dimensional shape. Sometimes these folded polypeptide chains are functional by themselves. Other times they combine with additional polypeptide chains to form the final protein structure. Sometimes non-polypeptide groups are also required in the final protein. For instance, the blood protein hemogobin is made up of four polypeptide chains, each of which also contains a heme molecule, which is ring structure with an iron atom in its center.
Proteins have different shapes and molecular weights, depending on the amino acid sequence. For example, hemoglobin is a globular protein, which means it folds into a compact globe-like structure, but collagen, found in our skin, is a fibrous protein, which means it folds into a long extended fiber-like chain. You probably look similar to your family members because you share similar proteins, but you look different from strangers because the proteins in your eyes, hair, and the rest of your body are different.
Because form determines function, any slight change to a protein’s shape may cause the protein to become dysfunctional. Small changes in the amino acid sequence of a protein can cause devastating genetic diseases such as Huntington’s disease or sickle cell anemia.
Enzymes
Enzymes are proteins that catalyze biochemical reactions, which otherwise would not take place. These enzymes are essential for chemical processes like digestion and cellular metabolism. Without enzymes, most physiological processes would proceed so slowly (or not at all) that life could not exist.
Because form determines function, each enzyme is specific to its substrates. The substrates are the reactants that undergo the chemical reaction catalyzed by the enzyme. The location where substrates bind to or interact with the enzyme is known as the active site, because that is the site where the chemistry occurs. When the substrate binds to its active site at the enzyme, the enzyme may help in its breakdown, rearrangement, or synthesis. By placing the substrate into a specific shape and microenvironment in the active site, the enzyme encourages the chemical reaction to occur. There are two basic classes of enzymes:
Enzyme reaction: A catabolic enzyme reaction showing the substrate matching the exact shape of the active site.
- Catabolic enzymes: enzymes that break down their substrate
- Anabolic enzymes: enzymes that build more complex molecules from their substrates
Enzymes are essential for digestion: the process of breaking larger food molecules down into subunits small enough to diffuse through a cell membrane and to be used by the cell. These enzymes include amylase, which catalyzes the digestion carbohydrates in the mouth and small intestine; pepsin, which catalyzes the digestion of proteins in the stomach; lipase, which catalyzes reactions need to emulsify fats in the small intestine; and trypsin, which catalyzes the further digestion of proteins in the small intestine.
Enzymes are also essential for biosynthesis: the process of making new, complex molecules from the smaller subunits that are provided to or generated by the cell. These biosynthetic enzymes include DNA Polymerase, which catalyzes the synthesis of new strands of the genetic material before cell division; fatty acid synthetase, which the synthesis of new fatty acids for fat or membrane lipid formation; and components of the ribosome, which catalyzes the formation of new polypeptides from amino acid monomers.
Hormones
Some proteins function as chemical-signaling molecules called hormones. These proteins are secreted by endocrine cells that act to control or regulate specific physiological processes, which include growth, development, metabolism, and reproduction. For example, insulin is a protein hormone that helps to regulate blood glucose levels. Other proteins act as receptors to detect the concentrations of chemicals and send signals to respond. Some types of hormones, such as estrogen and testosterone, are lipid steroids, not proteins.
Other Protein Functions
Tubulin: The structural protein tubulin stained red in mouse cells.
Proteins perform essential functions throughout the systems of the human body. In the respiratory system, hemoglobin (composed of four protein subunits) transports oxygen for use in cellular metabolism. Additional proteins in the blood plasma and lymph carry nutrients and metabolic waste products throughout the body. The proteins actin and tubulin form cellular structures, while keratin forms the structural support for the dead cells that become fingernails and hair. Antibodies, also called immunoglobins, help recognize and destroy foreign pathogens in the immune system. Actin and myosin allow muscles to contract, while albumin nourishes the early development of an embryo or a seedling.
Amino Acids
An amino acid contains an amino group, a carboxyl group, and an R group, and it combines with other amino acids to form polypeptide chains.
Learning Objectives
Describe the structure of an amino acid and the features that confer its specific properties
Key Takeaways
Key Points
- Each amino acid contains a central C atom, an amino group (NH2), a carboxyl group (COOH), and a specific R group.
- The R group determines the characteristics (size, polarity, and pH) for each type of amino acid.
- Peptide bonds form between the carboxyl group of one amino acid and the amino group of another through dehydration synthesis.
- A chain of amino acids is a polypeptide.
Key Terms
- amino acid: Any of 20 naturally occurring α-amino acids (having the amino, and carboxylic acid groups on the same carbon atom), and a variety of side chains, that combine, via peptide bonds, to form proteins.
- R group: The R group is a side chain specific to each amino acid that confers particular chemical properties to that amino acid.
- polypeptide: Any polymer of (same or different) amino acids joined via peptide bonds.
Structure of an Amino Acid
Amino acids are the monomers that make up proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, also known as the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. In the aqueous environment of the cell, the both the amino group and the carboxyl group are ionized under physiological conditions, and so have the structures -NH3+ and -COO–, respectively. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. This R group, or side chain, gives each amino acid proteins specific characteristics, including size, polarity, and pH.
Amino acid structure: 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. This amino acid is unionized, but if it were placed in water at pH 7, its amino group would pick up another hydrogen and a positive charge, and the hydroxyl in its carboxyl group would lose and a hydrogen and gain a negative charge.
Types of Amino Acids
The name “amino acid” is derived from the amino group and carboxyl-acid-group in their basic structure. There are 21 amino acids present in proteins, each with a specific R group or side chain. Ten of these are considered essential amino acids in humans because the human body cannot produce them and they must be obtained from the diet. All organisms have different essential amino acids based on their physiology.
Types of amino acids: There are 21 common amino acids commonly found in proteins, each with a different R group (variant group) that determines its chemical nature. The 21st amino acid, not shown here, is selenocysteine, with an R group of -CH2-SeH.
Characteristics of Amino Acids
Which categories of amino acid would you expect to find on the surface of a soluble protein, and which would you expect to find in the interior? What distribution of amino acids would you expect to find in a protein embedded in a lipid bilayer?
The chemical composition of the side chain determines the characteristics of the amino acid. Amino acids such as valine, methionine, and alanine are nonpolar (hydrophobic), while amino acids such as serine, threonine, and cysteine are polar (hydrophilic). The side chains of lysine and arginine are positively charged so these amino acids are also known as basic (high pH) amino acids. Proline is an exception to the standard structure of an amino acid because its R group is linked to the amino group, forming a ring-like structure.
Amino acids are represented by a single upper case letter or a three-letter abbreviation. For example, valine is known by the letter V or the three-letter symbol val.
Peptide Bonds
Peptide bond formation: Peptide bond formation is a dehydration synthesis reaction. The carboxyl group of one amino acid is linked to the amino group of the incoming amino acid. In the process, a molecule of water is released.
The sequence and the number of amino acids ultimately determine the protein’s shape, size, and function. Each amino acid is attached to another amino acid by a covalent bond, known as a peptide bond. When two amino acids are covalently attached by a peptide bond, the carboxyl group of one amino acid and the amino group of the incoming amino acid combine and release a molecule of water. Any reaction that combines two monomers in a reaction that generates H2O as one of the products is known as a dehydration reaction, so peptide bond formation is an example of a dehydration reaction.
Polypeptide Chains
The resulting chain of amino acids is called a polypeptide chain. Each polypeptide has a free amino group at one end. This end is called the N terminal, or the amino terminal, and the other end has a free carboxyl group, also known as the C or carboxyl terminal. When reading or reporting the amino acid sequence of a protein or polypeptide, the convention is to use the N-to-C direction. That is, the first amino acid in the sequence is assumed to the be one at the N terminal and the last amino acid is assumed to be the one at the C terminal.
Although the terms polypeptide and protein are sometimes used interchangeably, a polypeptide is technically any polymer of amino acids, whereas the term protein is used for a polypeptide or polypeptides that have folded properly, combined with any additional components needed for proper functioning, and is now functional.
Protein Structure
Each successive level of protein folding ultimately contributes to its shape and therefore its function.
Learning Objectives
Summarize the four levels of protein structure
Key Takeaways
Key Points
- Protein structure depends on its amino acid sequence and local, low-energy chemical bonds between atoms in both the polypeptide backbone and in amino acid side chains.
- Protein structure plays a key role in its function; if a protein loses its shape at any structural level, it may no longer be functional.
- Primary structure is the amino acid sequence.
- Secondary structure is local interactions between stretches of a polypeptide chain and includes α-helix and β-pleated sheet structures.
- Tertiary structure is the overall the three-dimension folding driven largely by interactions between R groups.
- Quarternary structures is the orientation and arrangement of subunits in a multi-subunit protein.
Key Terms
- antiparallel: The nature of the opposite orientations of the two strands of DNA or two beta strands that comprise a protein’s secondary structure
- disulfide bond: A bond, consisting of a covalent bond between two sulfur atoms, formed by the reaction of two thiol groups, especially between the thiol groups of two proteins
- β-pleated sheet: secondary structure of proteins where N-H groups in the backbone of one fully-extended strand establish hydrogen bonds with C=O groups in the backbone of an adjacent fully-extended strand
- α-helix: secondary structure of proteins where every backbone N-H creates a hydrogen bond with the C=O group of the amino acid four residues earlier in the same helix.
The shape of a protein is critical to its function because it determines whether the protein can interact with other molecules. Protein structures are very complex, and researchers have only very recently been able to easily and quickly determine the structure of complete proteins down to the atomic level. (The techniques used date back to the 1950s, but until recently they were very slow and laborious to use, so complete protein structures were very slow to be solved.) Early structural biochemists conceptually divided protein structures into four “levels” to make it easier to get a handle on the complexity of the overall structures. To determine how the protein gets its final shape or conformation, we need to understand these four levels of protein structure: primary, secondary, tertiary, and quaternary.
Primary Structure
A protein’s primary structure is the unique sequence of amino acids in each polypeptide chain that makes up the protein. Really, this is just a list of which amino acids appear in which order in a polypeptide chain, not really a structure. But, because the final protein structure ultimately depends on this sequence, this was called the primary structure of the polypeptide chain. For example, the pancreatic hormone insulin has two polypeptide chains, A and B.
Primary structure: The A chain of insulin is 21 amino acids long and the B chain is 30 amino acids long, and each sequence is unique to the insulin protein.
The gene, or sequence of DNA, ultimately determines the unique sequence of amino acids in each peptide chain. A change in nucleotide sequence of the gene’s coding region may lead to a different amino acid being added to the growing polypeptide chain, causing a change in protein structure and therefore function.
Sickle cell disease: Sickle cells are crescent shaped, while normal cells are disc-shaped.
The oxygen-transport protein hemoglobin consists of four polypeptide chains, two identical α chains and two identical β chains. In sickle cell anemia, a single amino substitution in the hemoglobin β chain causes a change the structure of the entire protein. When the amino acid glutamic acid is replaced by valine in the β chain, the polypeptide folds into an slightly-different shape that creates a dysfunctional hemoglobin protein. So, just one amino acid substitution can cause dramatic changes. These dysfunctional hemoglobin proteins, under low-oxygen conditions, start associating with one another, forming long fibers made from millions of aggregated hemoglobins that distort the red blood cells into crescent or “sickle” shapes, which clog arteries. People affected by the disease often experience breathlessness, dizziness, headaches, and abdominal pain.
Secondary Structure
A protein’s secondary structure is whatever regular structures arise from interactions between neighboring or near-by amino acids as the polypeptide starts to fold into its functional three-dimensional form. Secondary structures arise as H bonds form between local groups of amino acids in a region of the polypeptide chain. Rarely does a single secondary structure extend throughout the polypeptide chain. It is usually just in a section of the chain. The most common forms of secondary structure are the α-helix and β-pleated sheet structures and they play an important structural role in most globular and fibrous proteins.
Secondary structure: The α-helix and β-pleated sheet form because of hydrogen bonding between carbonyl and amino groups in the peptide backbone. Certain amino acids have a propensity to form an α-helix, while others have a propensity to form a β-pleated sheet.
In the α-helix chain, the hydrogen bond forms between the oxygen atom in the polypeptide backbone carbonyl group in one amino acid and the hydrogen atom in the polypeptide backbone amino group of another amino acid that is four amino acids farther along the chain. This holds the stretch of amino acids in a right-handed coil. Every helical turn in an alpha helix has 3.6 amino acid residues. The R groups (the side chains) of the polypeptide protrude out from the α-helix chain and are not involved in the H bonds that maintain the α-helix structure.
In β-pleated sheets, stretches of amino acids are held in an almost fully-extended conformation that “pleats” or zig-zags due to the non-linear nature of single C-C and C-N covalent bonds. β-pleated sheets never occur alone. They have to held in place by other β-pleated sheets. The stretches of amino acids in β-pleated sheets are held in their pleated sheet structure because hydrogen bonds form between the oxygen atom in a polypeptide backbone carbonyl group of one β-pleated sheet and the hydrogen atom in a polypeptide backbone amino group of another β-pleated sheet. The β-pleated sheets which hold each other together align parallel or antiparallel to each other. The R groups of the amino acids in a β-pleated sheet point out perpendicular to the hydrogen bonds holding the β-pleated sheets together, and are not involved in maintaining the β-pleated sheet structure.
Tertiary Structure
The tertiary structure of a polypeptide chain is its overall three-dimensional shape, once all the secondary structure elements have folded together among each other. Interactions between polar, nonpolar, acidic, and basic R group within the polypeptide chain create the complex three-dimensional tertiary structure of a protein. When protein folding takes place in the aqueous environment of the body, the hydrophobic R groups of nonpolar amino acids mostly lie in the interior of the protein, while the hydrophilic R groups lie mostly on the outside. Cysteine side chains form disulfide linkages in the presence of oxygen, the only covalent bond forming during protein folding. All of these interactions, weak and strong, determine the final three-dimensional shape of the protein. When a protein loses its three-dimensional shape, it will no longer be functional.
Tertiary structure: The tertiary structure of proteins is determined by hydrophobic interactions, ionic bonding, hydrogen bonding, and disulfide linkages.
Quaternary Structure
The quaternary structure of a protein is how its subunits are oriented and arranged with respect to one another. As a result, quaternary structure only applies to multi-subunit proteins; that is, proteins made from more than one polypeptide chain. Proteins made from a single polypeptide will not have a quaternary structure.
In proteins with more than one subunit, weak interactions between the subunits help to stabilize the overall structure. Enzymes often play key roles in bonding subunits to form the final, functioning protein.
For example, insulin is a ball-shaped, globular protein that contains both hydrogen bonds and disulfide bonds that hold its two polypeptide chains together. Silk is a fibrous protein that results from hydrogen bonding between different β-pleated chains.
Four levels of protein structure: The four levels of protein structure can be observed in these illustrations.
