Proteins: Properties, Structure, Types, Functions

Proteins are large, complex molecules essential for life. They are built from smaller subunits called amino acids, which act like Lego bricks to create an immense variety of structures with diverse functions.

Amino Acids:

Each amino acid has a central carbon atom bonded to four different groups:

• An amino group (NH2), which is basic (attracted to acids).
• A carboxyl group (COOH), which is acidic (attracted to bases).
• A hydrogen atom (H).
• A unique side chain (R group), which determines the specific properties of each amino acid.

The R group can be simple like a hydrogen atom or a methyl group (CH3), or more complex structures. Interestingly, all amino acids (except glycine) have an asymmetric carbon atom (alpha carbon) due to the unique R group. This asymmetry creates two mirror-image forms of the amino acid, much like your left and right hands. These forms are called D-amino acids and L-amino acids, distinguished by the position of the amino group (NH2) relative to the alpha carbon.

This ability to exist in two mirror-image forms is called chirality. Notably, only L-amino acids are typically used to build proteins in living organisms.

Amphoteric Molecules:

Amino acids possess both acidic and basic functional groups, making them amphoteric. This means they can act as acids or bases depending on the surrounding environment. They can exist as charged ions (except at a specific pH called the isoelectric point).

What are Proteins?

Proteins are complex molecules that play a critical role in every living organism.

Amino Acids

Proteins are built from smaller subunits called amino acids. Imagine them as Lego bricks that can be assembled in countless ways to create diverse structures. There are 20 different types of amino acids, each with a unique side chain (R group) that determines its specific properties. These amino acids link together to form long chains called polypeptides.

The Peptide Bonds

Amino acids are connected by strong chemical bonds known as peptide bonds. These bonds form between the amino group (NH2) of one amino acid and the carboxyl group (COOH) of another. A short chain of amino acids linked by peptide bonds is called a peptide. Peptides can be as small as two amino acids (dipeptides) or much longer, with polypeptides containing up to hundreds of amino acids.

Unique and Essential

Proteins are species-specific and even organ-specific. This means the protein makeup of your brain differs from that of your muscles. The specific sequence and arrangement of amino acids determine a protein’s unique shape and function.

Plants vs. Animals:

Interestingly, plants can synthesize all 20 essential amino acids needed to build proteins, while animals generally cannot. Animals must obtain some essential amino acids from their diet.

The Peptide Bond: Formation and Breakdown

The peptide bond is the backbone of proteins, linking amino acids together into long chains. Understanding how these bonds form and break is crucial for grasping protein structure and function.

A Dehydration Reaction

Peptide bond formation is a type of condensation reaction. This means two molecules come together, and a smaller molecule (water) is released. Here’s how it works:

1. The carboxyl group (COOH) of one amino acid gets close to the amino group (NH2) of another.
2. A chemical reaction occurs, where a hydroxyl group (OH) is removed from the first amino acid’s carboxyl group, and a hydrogen atom (H) is removed from the second amino acid’s amino group.
3. These removals combine to form a water molecule (H2O).
4. The remaining parts of the amino acids (carbon, nitrogen, and oxygen) link together to form a strong covalent bond called a peptide bond (C-N).

The resulting molecule with two linked amino acids is called a dipeptide. This process can be repeated numerous times, creating long chains of amino acids known as polypeptides.

Hydrolysis

Peptide bonds can also be broken down through a process called hydrolysis. This is the opposite of a condensation reaction, where a water molecule is added to break the bond. Here’s what happens:

1. A water molecule is inserted between the carbon-nitrogen (C-N) bond of the peptide linkage.
2. The water molecule is split, with its hydrogen attaching to the nitrogen atom and its hydroxyl group attaching to the carbon atom.
3. This cleavage separates the original peptide bond into two free amino acids, one with a terminal amino group (NH2) and the other with a terminal carboxyl group (COOH).

Hydrolysis of peptide bonds is crucial in many biological processes. Enzymes called proteases can specifically target and break peptide bonds, allowing for protein breakdown and recycling of amino acids within organisms.

What are polypeptides?

Polypeptides are nature’s protein architects. They are long, unbranched chains of amino acids linked by peptide bonds. Unlike shorter chains called peptides (which typically have less than ten amino acids), polypeptides can contain hundreds or even thousands of amino acids.

Linking Amino Acids

Each amino acid has a central carbon atom bonded to an amino group (NH2), a carboxyl group (COOH), and a unique side chain (R group). During polypeptide formation, the carboxyl group of one amino acid reacts with the amino group of another, forming a peptide bond. This process continues, adding amino acids one by one to the growing chain.

N- and C-terminals

A polypeptide has a distinct beginning and end. The amino-terminal (N-terminal) has a free amino group (NH2), while the carboxyl-terminal (C-terminal) has a free carboxyl group (COOH). These terminal ends play a crucial role in protein folding and function.

DNA to mRNA to Polypeptide

The specific sequence of amino acids in a polypeptide is determined by the genetic code. The instructions are carried in the DNA molecule, where specific sequences of nucleotides (genes) code for amino acids. During protein synthesis, this information is copied onto messenger RNA (mRNA) molecules. The mRNA codons are then “read” by ribosomes, which link the corresponding amino acids together to form the polypeptide chain.

Properties of Proteins

Water Solubility:

The interaction between proteins and water is complex and plays a critical role in protein structure. The secondary structure of a protein, formed by local folding patterns, depends on hydrogen bonds between peptide bonds and water molecules. Protein structures with high alpha-helical or beta-sheet content tend to be less soluble than globular structures with exposed hydrophilic (water-loving) regions.

At the tertiary structure level, water influences protein folding further. Hydrophobic (water-fearing) amino acid side chains tend to cluster within the protein interior, while hydrophilic side chains and the protein backbone orient towards the water environment. This arrangement is driven by the hydrophobic effect.

Denaturation and Renaturation:

Proteins can undergo a process called denaturation when exposed to factors like heat, radiation, extreme pH, or certain chemicals (urea, detergents). Denaturation disrupts the secondary and tertiary structures, causing the protein to unfold without breaking the peptide bonds (primary structure).

Interestingly, under certain conditions, a denatured protein might refold back into its original structure, a process called renaturation. This highlights the inherent stability of a protein’s primary structure.

Heat Coagulation:

When exposed to heat, some proteins (like albumins and globulins) undergo irreversible denaturation and form insoluble aggregates known as coagulum. This is why an egg white turns white and hardens when boiled. However, not all proteins are heat-sensitive.

Isoelectric Point:

Each protein has a unique isoelectric point (pI), a specific pH at which the molecule has no net electrical charge. This occurs when the number of positive charges (from amino acid side chains) is equal to the number of negative charges. At this pI, proteins are least soluble and won’t migrate in an electric field. This property is useful for protein isolation techniques.

Molecular Weight:

The size of a protein molecule is reflected in its molecular weight. This value is estimated by multiplying the average amino acid weight (around 110 Daltons) by the total number of amino acids in the protein. As expected, different proteins have varying molecular weights, ranging from a few thousand Daltons (small proteins) to millions of Daltons (large proteins).

Posttranslational Modifications:

After proteins are synthesized on ribosomes, they can undergo further modifications called posttranslational modifications. These modifications, such as phosphorylation (adding phosphate groups) or glycosylation (adding sugars), can alter the protein’s electrical charge, shape, and overall activity. These modifications are crucial for regulating protein function within cells.

Protein Structure

Proteins, complex macromolecules, have four fundamental structural levels: primary, secondary, tertiary, and quaternary. The first three levels can exist in single-chain proteins, while the fourth involves interactions between multiple polypeptide chains.

Protein Primary Structure

• Primary structure refers to the unique sequence of amino acids linked together by peptide bonds. Imagine a necklace where each bead represents a specific amino acid. This sequence is crucial for a protein’s properties and function.
• Peptide bonds, formed between the alpha-carboxyl group of one amino acid and the alpha-amino group of the next, connect these amino acids.
• The peptide bond has a partial double bond character due to resonance. This resonance effect stabilizes the bond, restricting rotation around the carbon-nitrogen (C-N) axis.
• While the C-N bond has limited rotation, other single bonds within the chain allow significant flexibility. This flexibility is essential for the protein to fold into more complex three-dimensional structures later.

Protein Secondary Structure

• Proteins start as linear chains of amino acids (primary structure), but these chains often fold into more complex shapes called secondary structures. This level describes the local folding patterns of the polypeptide chain, influenced by interactions between nearby amino acids.
• The key player in secondary structure formation is the hydrogen bond. These bonds form between the carbonyl oxygen (C=O) of one amino acid and the amino hydrogen (N-H) of another, often within the same polypeptide chain (intramolecular). This hydrogen bonding stabilizes the folded structure.
• Two main types of secondary structures arise from hydrogen bonding:
• Alpha helix: This resembles a spiral staircase. Here, hydrogen bonds form intramolecularly, between the carbonyl oxygen of an amino acid and the amino hydrogen of an amino acid four residues ahead in the chain. This creates a tightly coiled, right-handed helix.
• Beta sheet: Here, polypeptide chains lie side-by-side, linked by intermolecular hydrogen bonds. The chains can be arranged in parallel or antiparallel directions. In a beta sheet, the side chains (R groups) of the amino acids project alternately above and below the plane of the sheet.
• Secondary structures are crucial building blocks for the even more intricate three-dimensional (3D) structures of proteins (tertiary structure). Just like folded origami shapes become the foundation for more complex creations, secondary structures pave the way for protein function.

Tertiary Structure

• The tertiary structure is a protein’s unique 3D shape, formed by the folding of secondary structures. This folding is driven by:

• Hydrophobic interactions: Nonpolar side chains cluster inside, away from water.
• Other bonds: Hydrogen bonds, ionic bonds, and disulfide bridges stabilize the folded structure.

• This 3D shape determines a protein’s function. Two main types exist:

• Globular proteins: Compact and spherical, often enzymes or transport molecules.
• Fibrous proteins: Elongated and thread-like, providing structural support.

Protein Quaternary Structure

• This level applies only to proteins with multiple polypeptide chains (subunits). The quaternary structure describes how these subunits interact to form a complete functional protein. Imagine building a complex structure by assembling smaller units.

• Subunits are held together by various noncovalent bonds, such as:

• Hydrophobic interactions: Nonpolar side chains from different subunits cluster together, creating stability.
• Hydrogen bonds and ionic bonds: These interactions can form between subunits, further stabilizing the overall structure.

• Interestingly, these noncovalent bonds allow for some flexibility between subunits. This flexibility can be crucial for protein function, enabling conformational changes that activate or regulate the protein’s activity.

Protein Bonding

While peptide bonds are the building blocks of protein structure, other interactions play a crucial role in shaping and stabilizing protein molecules.

1. Hydrogen Bonds:

Hydrogen bonds form due to the attraction between a hydrogen atom bonded to a highly electronegative atom (like oxygen or nitrogen) and another electronegative atom. In proteins, hydrogen bonds can form between the carbonyl group (C=O) of one amino acid and the amino group (N-H) of another, often within the same polypeptide chain. These hydrogen bonds stabilize the secondary structure of proteins, particularly alpha helices and beta sheets.

2. Ionic Bonds:

Ionic bonds arise from the attraction between oppositely charged ions. In proteins, ionic bonds can form between acidic side chains (with negative charges) and basic side chains (with positive charges) of amino acids. While these interactions are weaker than hydrogen bonds, they contribute to stabilizing the overall three-dimensional (tertiary) structure of some globular proteins, particularly interactions with the surrounding environment.

3. Disulfide Bridges:

Disulfide bridges are the only other covalent bond besides peptide bonds found in proteins. They form between the side chains of two cysteine amino acids, where a sulfur atom from one cysteine forms a covalent bond with a sulfur atom from another. These strong covalent bonds significantly stabilize the tertiary structure of proteins, particularly providing rigidity and stability in certain proteins. However, unlike hydrogen bonds, disulfide bridges require specific conditions for formation and are more limited in their range of influence.

Hydrophobic and Hydrophilic Interactions

Proteins exist in an aqueous (watery) environment, and their interactions with water molecules are crucial. Two key forces play a significant role:

1. Hydrophobic Interactions:

Hydrophobic means “water-fearing.” Hydrophobic amino acid side chains (R groups) tend to cluster together within the protein’s interior, away from the surrounding water. This clustering minimizes the contact between these nonpolar side chains and water, creating a more stable structure. Think of it as oily droplets clustering together in water.

2. Hydrophilic Interactions:

Hydrophilic means “water-loving.” Amino acid side chains with polar or charged groups (often containing oxygen or nitrogen) tend to interact with water molecules through hydrogen bonds. These interactions position these hydrophilic groups on the protein’s surface, allowing the protein to dissolve in water.

Fibrous Proteins:

Fibrous proteins are aptly named for their elongated, thread-like structures. These sturdy proteins play a critical role in providing structural support and connective tissues throughout the body.

Collagen:

• Composition and Location:Collagen makes up a staggering 25-33% of all body proteins! It’s a key structural element found in connective tissues like tendons, cartilage, bones, and even the cornea of your eye.
• Unique Structure: Unlike the typical alpha helix, the collagen helix has a left-handed twist and packs three amino acid residues per turn. It’s also a triple helix, where three individual polypeptide chains (alpha chains) coil around each other to form a superhelix. This unique structure provides exceptional strength.
• Amino Acid Composition: Collagen is rich in specific amino acids, particularly glycine (35%), proline (21%), and hydroxyproline (4-hydroxyproline). These amino acids contribute to collagen’s unique structure and stability.

Keratin:

• Another important fibrous protein is keratin, also known as alpha-keratin. This protein makes up a significant portion of hair, nails, skin, and other tough structures in mammals.
• Keratin belongs to a broader group called intermediate filament (IF) proteins. These proteins play a crucial role in maintaining the shape and integrity of cells.
• Secondary Structure: Unlike collagen, keratin’s basic building block is the right-handed alpha helix, a common structural element in many proteins.
• The Coiled-Coil: Two keratin strands, arranged in parallel, twist around each other to form a super-coiled structure. This coiling significantly strengthens the overall protein.
• Individual Strands: At the tertiary level, each keratin polypeptide within the coiled-coil has a relatively simple structure dominated by the right-handed alpha helix. However, the entire coiled-coil itself twists slightly to the left, creating a left-handed superhelix.
• Intertwined Strength: The interaction between the two alpha-helical polypeptides in keratin exemplifies a quaternary structure. This intertwining further contributes to the strength and stability of keratin.

Elastin:

• Elastin is a fascinating fibrous protein found in tissues that require elasticity, such as lungs, bladders, and elastic cartilage. Unlike collagen and keratin with their well-defined structures, elastin offers a unique twist.
• Polypeptide Chain: Elastin is made up of tropoelastin protein, rich in amino acids like glycine, valine, and modified alanine and proline. This composition allows for flexibility.
• No Ordinary Helix: Unlike collagen’s rigid triple helix or keratin’s alpha helices, elastin lacks a regular secondary structure. This gives elastin greater flexibility to stretch and recoil.
• Strength in Numbers: Elastin’s magic lies in its cross-links. These are chemical connections between various protein sequences, forming a network throughout the elastin molecule. These cross-links provide strength and elasticity without a rigid structure.
• While elastin shares an abundance of glycine and proline with collagen, the arrangement is distinct. Unlike collagen’s glycine at every third residue, elastin’s glycine and proline are scattered throughout the chain, contributing to its unique flexibility.

Globular Proteins

Hemoglobin:

• Hemoglobin is the essential protein found in red blood cells, responsible for transporting oxygen throughout the body. It makes up a whopping 90% of the protein content within these red blood cells.
• Hemoglobin is a tetrameric protein, meaning it has four polypeptide chains working together. These chains are not identical – two are called alpha (α) chains, and the other two are beta (β) chains.
• Each alpha and beta chain contains sections folded into alpha helices. These helices are held together within each chain by ionic bonds and hydrogen bonds, creating a stable structure.
• The four polypeptide chains (two alpha and two beta) come together in a specific arrangement, resembling a tetrahedron. This assembly of chains is stabilized by noncovalent interactions, forming the characteristic quaternary structure of hemoglobin.

Insulin:

• Insulin, a peptide hormone produced by the pancreas, plays a critical role in regulating how our bodies manage carbohydrates, fats, and proteins.
• The Stable Form: Insulin is initially stored in the pancreas in an inactive form called a hexamer. This six-unit structure (hexa means six) helps to keep the insulin protein stable and protected.
• The Active Form: When the body needs to regulate blood sugar levels, the hexamer breaks down, releasing the active form of insulin, a single protein monomer.
• Building Blocks: Each insulin monomer is made of 51 amino acids linked together to form two polypeptide chains.
• Disulfide Bonds: These two chains are held together by strong covalent bonds called disulfide bridges.
• Folding Patterns: One chain has two alpha-helix structures, while the other has an alpha-helix and two beta-sheet structures. These specific folding patterns contribute to insulin’s function.
• Species Similarities: Interestingly, the amino acid sequence in insulin is highly conserved across different species, meaning it changes very little between animals. This highlights the crucial role insulin plays in maintaining life.

Pepsin:

• Pepsin is a digestive enzyme superstar in our stomachs. Its job? To break down proteins into smaller, more manageable pieces called peptides and amino acids. Pepsin is one of three important digestive proteases (protein-cutting enzymes) alongside trypsin and chymotrypsin.

• Inactive to Active: Pepsin is actually released by stomach wall cells in an inactive form called pepsinogen. This protects the stomach lining from being digested by its own enzyme!
• When food enters the stomach, it mixes with hydrochloric acid. This acidic environment activates pepsinogen, converting it into the active enzyme pepsin.
• Pepsin’s primary function is aided by its structure:
• The predominant secondary structure in pepsin is beta-sheets. These sheets provide a stable scaffold for the enzyme.
• Six right-handed alpha-helices are also present, likely contributing to the enzyme’s active site where protein breakdown occurs.
• Interestingly, pepsin is also a component of rennet, a substance used in cheesemaking. Rennet helps curdle milk, an essential step in cheese production.

Glycoproteins:

• Glycoproteins are a fascinating class of proteins that partner with carbohydrates (sugars) to create unique molecules. These sugars aren’t just random decorations; they play a crucial role in a glycoprotein’s function.
• Glycoproteins have carbohydrates attached as a prosthetic group, meaning a non-amino acid component essential for function.
• The amount of sugar varies, but it’s typically less than 4% of the total molecule.
• Many glycoproteins are integral membrane proteins, meaning they are embedded in the cell membrane. These glycoproteins help cells recognize each other and interact through cell-to-cell signaling.
• Immunoglobulins, also known as antibodies, are essential glycoproteins in the immune system. The sugars on these antibodies help them target and neutralize specific pathogens.
• Soluble glycoproteins are also found throughout the body, including in egg albumin (egg white) and blood plasma. These soluble glycoproteins can have various functions depending on their specific structure.

Lipoproteins:

• Lipoproteins are a special class of proteins that team up with lipids (fats) like cephalin, lecithin, and cholesterol. This partnership allows them to perform a vital task: transporting fats throughout the body.

• Unique Solubility: Unlike most fats, which are insoluble in water, lipoproteins can dissolve in water. This is because the protein portion of the lipoprotein is hydrophilic (water-loving), allowing it to interact with water.
• Inner Workings: Inside the lipoprotein, the lipid molecules are tucked away in a hydrophobic (water-fearing) core. This core is shielded from water by the surrounding protein shell.
• Lipoproteins act as temporary carriers, shuttling fats from their absorption sites in the intestine to various tissues throughout the body that need them for energy or cell building.
• Scientists classify lipoproteins into four main groups based on their density. This classification helps differentiate them based on their size, lipid content, and specific functions.

Protein Denaturation

• Proteins are amazing molecules that work efficiently because of their precise three-dimensional structures. However, these structures can be disrupted in a process called denaturation.
• Denaturation occurs when a protein is exposed to external stresses, such as:
• Heat: High temperatures can disrupt the weak hydrogen bonds that hold a protein’s structure in place, causing it to unfold.
• Strong chemicals: Acids, bases, and some organic solvents can also disrupt these bonds and denature proteins.
• Denaturation can have significant consequences for a protein’s function:
• Loss of Activity: When a protein unfolds, it loses its original shape and can no longer bind to other molecules or perform its intended function. This can disrupt essential cellular processes.
• Reduced Solubility: Denatured proteins often clump together and become insoluble in water. This aggregation can damage cells and tissues.
• The good news is that in some cases, denaturation can be reversed. If the stressor is removed, the protein might refold back into its original shape and regain its function. This is called renaturation.
• Unfortunately, some forms of denaturation are irreversible. This often happens when the protein chain itself is broken or when strong covalent bonds are disrupted.

A Classification of Proteins

1. Simple Proteins:

• Two Main Types:
  • Fibrous Proteins: Elongated and thread-like, providing structural support (e.g., keratin in hair, collagen in connective tissues).
  • Globular Proteins: Compact and spherical, often with enzymatic or transport functions (e.g., albumin in blood, globulin in immune system).

2. Conjugated Proteins:

• These proteins team up with a non-protein group called a prosthetic group. This partnership gives them unique functions.
• Examples:
  • Nucleoproteins (protein + nucleic acid) – found in chromosomes
  • Lipoproteins (protein + lipids) – transport fats in blood
  • Metalloproteins (protein + metal ion) – some enzymes require metal ions for activity

3. Derived Proteins:

• Breakdown Products: Formed when simple or conjugated proteins undergo modifications or break down.
• Two Subcategories:
  • Primary Derived Proteins: Relatively large fragments resulting from the initial breakdown. (e.g., proteans)
  • Secondary Derived Proteins: Smaller fragments or peptides resulting from further breakdown. (e.g., peptones)

The Function of Proteins

• Many proteins act as enzymes, speeding up essential chemical reactions within cells. These reactions would occur too slowly without enzymes, hindering vital metabolic processes.
• Fibrous proteins, such as collagen, provide structural support and connective tissues. They act like the body’s scaffolding, holding bones, muscles, and other tissues together.
• Nucleoproteins, a type of conjugated protein, safeguard our genetic material. They package DNA within chromosomes, ensuring its proper inheritance.
• Specific proteins act as transporters, facilitating the movement of various molecules (ions, nutrients) across cell membranes. They regulate what enters and exits cells, maintaining essential cellular balance.
• Protein hormones are vital chemical messengers that coordinate diverse physiological functions, such as growth, development, and metabolism.
• Some proteins play a crucial role in defense. Interferons, for example, are proteins produced in response to viruses or infections, helping to fight off invaders. Additionally, defensins, a type of peptide (short protein chain) act as natural antibiotics, providing further protection.
• Blood plasma contains several soluble proteins that can be used in medical treatments. These proteins can help restore fluids and balance electrolytes in individuals suffering from shock due to injury or surgery.