Proteins Are Made Of Monomers Called

Proteins, the workhorses of the cell, are essential for virtually every biological process. Understanding their fundamental building blocks, the monomers that comprise them, is crucial to comprehending their diverse functions. These monomers are called amino acids, and they link together in specific sequences to form the complex structures of proteins.

The Foundation: Amino Acids

Amino acids are organic molecules that contain a central carbon atom bonded to four different groups:

• An amino group (-NH2)
• A carboxyl group (-COOH)
• A hydrogen atom (-H)
• A variable side chain (R-group)

It is the R-group that distinguishes one amino acid from another, giving each unique chemical properties. There are 20 standard amino acids commonly found in proteins, each with its own unique R-group. These R-groups vary in size, shape, charge, hydrophobicity, and reactivity, contributing to the diverse functions of proteins.

Classifying Amino Acids

Amino acids can be classified based on the properties of their R-groups. Here are some common classifications:

• Nonpolar, Aliphatic R-groups: These amino acids have hydrophobic R-groups composed of carbon and hydrogen. Examples include alanine, valine, leucine, and isoleucine. They tend to cluster together within proteins, away from the aqueous environment.
• Aromatic R-groups: These amino acids contain aromatic rings in their R-groups. Examples include phenylalanine, tyrosine, and tryptophan. They are relatively nonpolar and can participate in hydrophobic interactions. Tyrosine and tryptophan can also absorb ultraviolet light.
• Polar, Uncharged R-groups: These amino acids have polar R-groups that can form hydrogen bonds with water and other polar molecules. Examples include serine, threonine, cysteine, asparagine, and glutamine. Cysteine can also form disulfide bonds with other cysteine residues, contributing to protein stability.
• Positively Charged (Basic) R-groups: These amino acids have positively charged R-groups at physiological pH. Examples include lysine, arginine, and histidine. They are hydrophilic and often found on the surface of proteins.
• Negatively Charged (Acidic) R-groups: These amino acids have negatively charged R-groups at physiological pH. Examples include aspartate and glutamate. They are also hydrophilic and often found on the surface of proteins.

The Peptide Bond: Linking Amino Acids Together

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

The formation of a peptide bond results in a dipeptide. Adding more amino acids creates a tripeptide, a tetrapeptide, and so on. A chain of many amino acids linked by peptide bonds is called a polypeptide. Proteins are typically composed of one or more polypeptide chains.

The peptide bond has partial double-bond character due to resonance, which makes it rigid and planar. This rigidity restricts the flexibility of the polypeptide chain and influences its folding.

From Polypeptide to Functional Protein: Levels of Protein Structure

The sequence of amino acids in a polypeptide chain determines its three-dimensional structure and, ultimately, its function. Protein structure is organized into four levels:

• Primary Structure: This is the linear sequence of amino acids in the polypeptide chain. It is determined by the genetic code and is unique for each protein. The primary structure dictates all subsequent levels of structure.
• Secondary Structure: This refers to the local folding patterns of the polypeptide chain, stabilized by hydrogen bonds between the amino and carboxyl groups of the peptide backbone. The two most common secondary structures are the alpha helix and the beta sheet.
  • Alpha Helix: A helical structure formed by hydrogen bonds between every fourth amino acid. The R-groups extend outward from the helix.
  • Beta Sheet: A sheet-like structure formed by hydrogen bonds between adjacent polypeptide strands. The strands can be parallel or antiparallel, depending on their orientation.
• Tertiary Structure: This is the overall three-dimensional shape of a single polypeptide chain, resulting from interactions between the R-groups of amino acids. These interactions include:
  • Hydrogen bonds
  • Ionic bonds
  • Hydrophobic interactions
  • Disulfide bonds
• Quaternary Structure: This is the arrangement of multiple polypeptide chains (subunits) in a multi-subunit protein. Not all proteins have quaternary structure. The subunits are held together by the same types of interactions that stabilize tertiary structure.

The proper folding of a protein is crucial for its function. Misfolded proteins can aggregate and cause diseases such as Alzheimer's disease and Parkinson's disease.

Protein Functions: A Diverse Array of Roles

Proteins perform a vast array of functions in living organisms. Here are some examples:

• Enzymes: Catalyze biochemical reactions.
• Structural Proteins: Provide support and shape to cells and tissues (e.g., collagen, keratin).
• Transport Proteins: Carry molecules across cell membranes or throughout the body (e.g., hemoglobin, albumin).
• Motor Proteins: Facilitate movement (e.g., myosin, kinesin).
• Antibodies: Recognize and bind to foreign substances (antigens) as part of the immune response.
• Hormones: Chemical messengers that regulate various physiological processes (e.g., insulin, growth hormone).
• Receptor Proteins: Bind to signaling molecules and initiate cellular responses.
• Storage Proteins: Store nutrients (e.g., ferritin stores iron).

The specific function of a protein depends on its amino acid sequence and its three-dimensional structure. Even a single amino acid change can alter protein structure and function, sometimes with devastating consequences.

Protein Synthesis: From DNA to Protein

The process of protein synthesis, also known as translation, occurs in ribosomes and involves the following steps:

1. Transcription: DNA is transcribed into messenger RNA (mRNA) in the nucleus. The mRNA molecule carries the genetic code from the DNA to the ribosome.
2. Initiation: The mRNA binds to the ribosome, and the first transfer RNA (tRNA) molecule, carrying the amino acid methionine, binds to the start codon (AUG) on the mRNA.
3. Elongation: The ribosome moves along the mRNA, codon by codon. For each codon, a tRNA molecule carrying the corresponding amino acid binds to the mRNA. The amino acid is added to the growing polypeptide chain through the formation of a peptide bond.
4. Termination: The ribosome reaches a stop codon (UAA, UAG, or UGA) on the mRNA. There is no tRNA that corresponds to the stop codon. Instead, a release factor binds to the ribosome, causing the polypeptide chain to be released.
5. Post-translational Modification: The newly synthesized polypeptide chain may undergo further modifications, such as folding, glycosylation (addition of sugars), or phosphorylation (addition of phosphate groups), to become a functional protein.

Beyond the 20: Non-Standard Amino Acids

While proteins are primarily constructed from 20 standard amino acids, there are also non-standard amino acids that can be incorporated into proteins or found in other biological molecules. These non-standard amino acids are typically formed by post-translational modification of standard amino acids. Examples include:

• Hydroxyproline: Formed by hydroxylation of proline and found in collagen.
• Hydroxylysine: Formed by hydroxylation of lysine and also found in collagen.
• gamma-Carboxyglutamate: Formed by carboxylation of glutamate and involved in blood clotting.
• Selenocysteine: Incorporated into proteins at specific UGA codons and contains selenium instead of sulfur.

These non-standard amino acids contribute to the diversity and complexity of protein function.

Nutritional Importance of Amino Acids

Amino acids are essential nutrients for humans and other animals. We can synthesize some amino acids from other molecules, but others, called essential amino acids, must be obtained from our diet. The nine essential amino acids are:

• Histidine
• Isoleucine
• Leucine
• Lysine
• Methionine
• Phenylalanine
• Threonine
• Tryptophan
• Valine

A diet lacking in one or more essential amino acids can lead to malnutrition and various health problems. Protein-rich foods such as meat, poultry, fish, eggs, dairy products, legumes, and nuts are important sources of amino acids.

Understanding Amino Acids: Key to Understanding Life

The study of amino acids and proteins is fundamental to understanding the molecular basis of life. From catalyzing biochemical reactions to providing structural support, proteins perform a vast array of functions essential for living organisms. By understanding the building blocks of proteins, the amino acids, and how they are linked together to form complex structures, we can gain insights into the mechanisms of disease, develop new therapies, and advance our understanding of the biological world.

Common Modifications to Amino Acids After Protein Synthesis

After a protein is synthesized, its amino acids can undergo various modifications that alter its function, location, or interaction with other molecules. These modifications, often called post-translational modifications (PTMs), vastly expand the functional diversity of the proteome. Here are a few common examples:

• Phosphorylation: The addition of a phosphate group to serine, threonine, or tyrosine residues. This is a highly common regulatory mechanism, often turning enzymes "on" or "off" in response to cellular signals. Kinases are the enzymes that catalyze phosphorylation, while phosphatases remove phosphate groups.

• Glycosylation: The attachment of a sugar molecule (glycan) to asparagine (N-linked) or serine/threonine (O-linked) residues. Glycosylation can affect protein folding, stability, localization, and interactions. It's particularly important for proteins on the cell surface and secreted proteins.

• Ubiquitination: The addition of ubiquitin, a small protein, to lysine residues. Ubiquitination can signal for protein degradation by the proteasome, alter protein activity, or affect protein localization and interactions.

• Acetylation: The addition of an acetyl group to lysine residues, often affecting histone proteins and influencing gene expression. Acetylation generally leads to a more open chromatin structure and increased transcription.

• Methylation: The addition of a methyl group to lysine or arginine residues, also commonly affecting histone proteins and influencing gene expression. Methylation can either activate or repress gene transcription, depending on the specific residue methylated and the surrounding context.

• Lipidation: The attachment of lipid molecules to proteins, often targeting proteins to cellular membranes. Common types include myristoylation, palmitoylation, and prenylation.

• Proteolytic Cleavage: The removal of a portion of a protein, often to activate it. For example, many enzymes are synthesized as inactive precursors (zymogens) that are activated by proteolytic cleavage. Insulin is another example, where the initial preproinsulin molecule is cleaved multiple times to produce the mature, active hormone.

These are just a few examples of the many types of post-translational modifications that can occur. The specific modifications that a protein undergoes depend on the protein itself, the cellular context, and the environmental conditions. These modifications are essential for regulating protein function and responding to cellular needs.

The Genetic Code: Dictating the Amino Acid Sequence

The sequence of amino acids in a protein is directly determined by the genetic code, which is a set of rules that specifies how the information encoded in DNA is translated into protein. The genetic code is based on codons, which are three-nucleotide sequences in mRNA that each specify a particular amino acid (or a start or stop signal).

There are 64 possible codons (4 nucleotides taken 3 at a time: 4 x 4 x 4 = 64). Of these:

• 61 codons specify amino acids.
• 1 codon (AUG) serves as the start codon, initiating translation. It also codes for methionine.
• 3 codons (UAA, UAG, UGA) are stop codons, signaling the end of translation.

The genetic code is degenerate, meaning that most amino acids are specified by more than one codon. This redundancy provides some protection against the effects of mutations. However, a mutation that changes a codon can still lead to a different amino acid being incorporated into the protein, potentially altering its function.

The genetic code is also nearly universal, meaning that it is used by almost all living organisms. This suggests that the genetic code evolved very early in the history of life and has been highly conserved.

Amino Acid Analogs and Inhibitors

Amino acid analogs are molecules that are structurally similar to amino acids but have slight differences. These analogs can sometimes be incorporated into proteins during synthesis, leading to non-functional or toxic proteins. Other analogs can act as inhibitors of enzymes involved in amino acid metabolism or protein synthesis. Some amino acid analogs are used as drugs. For example:

• Azaserine: A glutamine analog that inhibits enzymes involved in purine biosynthesis and is used as an anticancer drug.
• Puromycin: A tRNA analog that terminates protein synthesis and is used as an antibiotic.

Conclusion

Amino acids are the fundamental monomers that make up proteins, the workhorses of the cell. Their diverse chemical properties, dictated by their R-groups, contribute to the vast array of protein functions. Understanding the structure, function, and synthesis of proteins is crucial for understanding the molecular basis of life and for developing new therapies for disease. The precise sequence of amino acids, dictated by the genetic code, determines the unique three-dimensional structure and, ultimately, the function of each protein. From enzymes that catalyze biochemical reactions to structural proteins that provide support, proteins are essential for virtually every biological process.