What Molecules Make Up A Protein

Proteins are the workhorses of our cells, carrying out a vast array of functions essential for life. But what are these complex molecules made of? Understanding the fundamental building blocks of proteins is crucial to appreciating their diverse roles and intricate mechanisms.

The Foundation: Amino Acids

Proteins are essentially long chains of amino acids, linked together in a specific sequence. Think of amino acids as the alphabet, and proteins as the words you can create from that alphabet. The order of these amino acids dictates the protein's unique structure and, consequently, its function.

The Structure of an Amino Acid

Each amino acid shares a common core structure consisting of:

A central carbon atom (the alpha carbon).
An amino group (-NH2).
A carboxyl group (-COOH).
A hydrogen atom (-H).
And a variable side chain (or R-group).

The R-group is the key to the unique properties of each amino acid. It's what differentiates one amino acid from another, influencing its size, shape, charge, hydrophobicity (tendency to repel water), and reactivity.

The 20 Standard Amino Acids

While there are hundreds of amino acids found in nature, only 20 are commonly used in the genetic code to build proteins in most organisms. These are often referred to as the 20 standard amino acids or the proteinogenic amino acids. Each has a unique R-group, contributing to the diverse range of protein structures and functions. These 20 amino acids are:

Alanine (Ala, A): A simple, hydrophobic amino acid with a methyl group as its R-group.
Arginine (Arg, R): A positively charged (basic) amino acid with a complex R-group containing a guanidinium group.
Asparagine (Asn, N): A polar amino acid with an amide group in its R-group.
Aspartic Acid (Asp, D): A negatively charged (acidic) amino acid with a carboxyl group in its R-group.
Cysteine (Cys, C): A polar amino acid containing a thiol (-SH) group in its R-group, which can form disulfide bonds with other cysteine residues.
Glutamine (Gln, Q): A polar amino acid with an amide group in its R-group, similar to asparagine.
Glutamic Acid (Glu, E): A negatively charged (acidic) amino acid with a carboxyl group in its R-group, similar to aspartic acid.
Glycine (Gly, G): The simplest amino acid with only a hydrogen atom as its R-group. This allows for greater flexibility in the protein backbone.
Histidine (His, H): A positively charged (basic) amino acid with an imidazole ring in its R-group. Its charge can vary depending on the pH.
Isoleucine (Ile, I): A hydrophobic amino acid with a branched aliphatic R-group.
Leucine (Leu, L): A hydrophobic amino acid with a branched aliphatic R-group, similar to isoleucine.
Lysine (Lys, K): A positively charged (basic) amino acid with an amino group in its R-group.
Methionine (Met, M): A hydrophobic amino acid containing a sulfur atom in its R-group. Often the first amino acid in a newly synthesized protein.
Phenylalanine (Phe, F): A hydrophobic amino acid with a phenyl ring in its R-group.
Proline (Pro, P): A unique amino acid whose R-group is cyclic and bonded to the amino group, creating a rigid structure that disrupts alpha-helices.
Serine (Ser, S): A polar amino acid with a hydroxyl group (-OH) in its R-group, which can be phosphorylated.
Threonine (Thr, T): A polar amino acid with a hydroxyl group (-OH) in its R-group, similar to serine, and can also be phosphorylated.
Tryptophan (Trp, W): A hydrophobic amino acid with a large, bulky indole ring in its R-group.
Tyrosine (Tyr, Y): A polar amino acid with a phenyl ring and a hydroxyl group (-OH) in its R-group, which can be phosphorylated.
Valine (Val, V): A hydrophobic amino acid with a branched aliphatic R-group, similar to leucine and isoleucine.

Classifying Amino Acids

Amino acids are often classified based on the properties of their R-groups:

Nonpolar, Hydrophobic Amino Acids: These amino acids have R-groups that are primarily composed of carbon and hydrogen atoms. They tend to cluster together in the interior of proteins, away from water. Examples include alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, and methionine. Glycine is also usually included in this group due to its small size and non-polar nature.
Polar, Hydrophilic Amino Acids: These amino acids have R-groups that contain atoms like oxygen, nitrogen, or sulfur, which can form hydrogen bonds with water. They are often found on the surface of proteins, interacting with the aqueous environment. Examples include serine, threonine, cysteine, tyrosine, asparagine, and glutamine.
Charged Amino Acids: These amino acids have R-groups that are either positively charged (basic) or negatively charged (acidic) at physiological pH. They are strongly hydrophilic and often participate in ionic interactions. The positively charged amino acids are lysine, arginine, and histidine. The negatively charged amino acids are aspartic acid and glutamic acid.

Building the Chain: Peptide Bonds

Amino acids are linked together to form a polypeptide chain through peptide bonds. A peptide bond is a covalent bond formed between the carboxyl group of one amino acid and the amino group of the next amino acid, with the removal of a water molecule (H2O). This process is called dehydration or condensation.

The Polypeptide Backbone

The repeating sequence of the amino group, alpha carbon, and carboxyl group in each amino acid forms the polypeptide backbone. This backbone is common to all proteins and provides the structural framework for the protein. The R-groups of the amino acids extend outward from the backbone, interacting with each other and the surrounding environment.

From Polypeptide to Protein

A polypeptide is simply a chain of amino acids linked by peptide bonds. However, a polypeptide is not necessarily a functional protein. To become a functional protein, the polypeptide chain must fold into a specific three-dimensional structure. This folding process is guided by interactions between the amino acid R-groups and the surrounding environment.

Beyond Amino Acids: Additional Components

While amino acids are the primary building blocks of proteins, some proteins also contain other molecules that are essential for their structure and function. These additional components are often referred to as prosthetic groups, cofactors, or coenzymes.

Prosthetic Groups

Prosthetic groups are non-amino acid components that are tightly bound to a protein and are essential for its activity. They can be organic molecules, such as heme in hemoglobin, or metal ions, such as iron in cytochromes.

Heme: A porphyrin ring complex containing iron, found in hemoglobin and myoglobin. It is responsible for binding oxygen.
Biotin: A vitamin that serves as a cofactor for carboxylase enzymes.
Flavin adenine dinucleotide (FAD): A redox-active coenzyme derived from riboflavin (vitamin B2).
Pyridoxal phosphate (PLP): A coenzyme derived from pyridoxine (vitamin B6), involved in amino acid metabolism.

Cofactors

Cofactors are inorganic ions or organic molecules that are required for the activity of certain enzymes. They bind to the enzyme and help it to catalyze a reaction. Unlike prosthetic groups, cofactors are not tightly bound to the protein.

Metal ions: Many enzymes require metal ions such as zinc, magnesium, iron, copper, or manganese for their activity. These ions can participate in catalysis by stabilizing transition states or by acting as Lewis acids or bases.
Coenzymes: Organic molecules that bind to enzymes and help them to catalyze reactions. They are often derived from vitamins. Examples include:
- Nicotinamide adenine dinucleotide (NAD+): A redox-active coenzyme derived from niacin (vitamin B3).
- Coenzyme A (CoA): Involved in the transfer of acyl groups.
- Tetrahydrofolate (THF): A coenzyme involved in the transfer of one-carbon units.

Glycoproteins and Lipoproteins

Some proteins are modified by the addition of carbohydrates or lipids. These are known as glycoproteins and lipoproteins, respectively.

Glycoproteins: Proteins that have one or more carbohydrate chains covalently attached to them. Glycosylation can affect protein folding, stability, and interactions with other molecules. Many cell surface proteins are glycoproteins.
Lipoproteins: Proteins that are associated with lipids. Lipoproteins are involved in the transport of lipids in the blood. Examples include high-density lipoprotein (HDL) and low-density lipoprotein (LDL).

The Importance of Structure: Levels of Protein Organization

The structure of a protein is critical to its function. Proteins have four levels of structural organization: primary, secondary, tertiary, and quaternary.

Primary Structure

The primary structure of a protein is simply the sequence of amino acids in the polypeptide chain. This sequence is determined by the genetic code. Even a single amino acid change can have a significant impact on the protein's structure and function.

Secondary Structure

The secondary structure refers to the local folding patterns of the polypeptide backbone. The two most common secondary structures are the alpha-helix and the beta-sheet. These structures are stabilized by hydrogen bonds between the carbonyl oxygen and the amide hydrogen atoms in the polypeptide backbone.

Alpha-helix: A helical structure in which the polypeptide backbone is coiled around an imaginary axis. The R-groups of the amino acids extend outward from the helix.
Beta-sheet: A sheet-like structure in which two or more polypeptide chains (or segments of the same chain) are aligned side-by-side. The chains can be parallel or antiparallel.

Tertiary Structure

The tertiary structure is the overall three-dimensional shape of a single polypeptide chain. It is determined by interactions between the R-groups of the amino acids, including hydrogen bonds, ionic bonds, hydrophobic interactions, and disulfide bonds.

Quaternary Structure

The quaternary structure refers to the arrangement of multiple polypeptide chains (subunits) in a multi-subunit protein. Not all proteins have quaternary structure. Hemoglobin, for example, has a quaternary structure consisting of four subunits.

Factors Affecting Protein Structure and Function

Many factors can affect protein structure and function, including:

Temperature: High temperatures can denature proteins, causing them to unfold and lose their activity.
pH: Changes in pH can alter the charge of amino acid R-groups, affecting their interactions and protein structure.
Salt concentration: High salt concentrations can disrupt ionic bonds and hydrophobic interactions, affecting protein structure.
Solvents: Organic solvents can disrupt hydrophobic interactions and denature proteins.
Chaperone proteins: These proteins assist in the proper folding of other proteins, preventing misfolding and aggregation.

Common Questions About Protein Molecules

What happens if a protein misfolds?

Misfolded proteins can aggregate and form insoluble clumps, which can be toxic to cells. Some diseases, such as Alzheimer's and Parkinson's, are associated with the accumulation of misfolded proteins.
Can proteins be synthesized in the lab?

Yes, proteins can be synthesized in the lab using chemical methods or by expressing the protein in a host organism, such as bacteria or yeast.
How are proteins broken down?

Proteins are broken down into amino acids by enzymes called proteases. This process occurs in the stomach, intestines, and lysosomes.
Are all proteins enzymes?

No, not all proteins are enzymes. Enzymes are proteins that catalyze biochemical reactions. However, proteins also have many other functions, such as structural support, transport, and signaling.
Why is the sequence of amino acids so important?

The sequence of amino acids determines the protein's three-dimensional structure, which in turn determines its function. Even a single amino acid change can have a significant impact on the protein's activity.

In Conclusion

Proteins are built from a foundation of amino acids, linked together by peptide bonds. The unique properties of the 20 standard amino acids, along with additional components like prosthetic groups and cofactors, contribute to the incredible diversity of protein structures and functions. Understanding the molecules that make up a protein is essential for comprehending the complexity of life and for developing new therapies for disease. From catalyzing reactions to providing structural support, proteins are the molecular machines that drive the cellular processes necessary for life.