Proteins Are Built From Simpler Organic Compounds Called

Proteins, the workhorses of our cells, are vital for countless functions, from catalyzing biochemical reactions to transporting molecules and providing structural support. Understanding what they're made of is key to understanding how they work. Proteins are constructed from smaller organic molecules known as amino acids. These amino acids, linked together in specific sequences, form the diverse array of proteins that dictate life processes.

Decoding the Building Blocks: Amino Acids

Amino acids are organic compounds containing both an amino group (-NH2) and a carboxyl group (-COOH), along with a side chain (R group) that is unique to each amino acid. This central carbon atom, bonded to these groups, gives each amino acid its distinct characteristics.

• The General Structure: All amino acids share a common backbone structure consisting of a central carbon atom (the α-carbon) bonded to:
  • An amino group (-NH2)
  • A carboxyl group (-COOH)
  • A hydrogen atom (-H)
  • A distinctive side chain (R group)
• The Unique R Group: What differentiates one amino acid from another is the R group. This side chain varies in structure, size, electrical charge, and hydrophobicity (its affinity for water). These variations in R groups are what give each amino acid its unique chemical properties and influence the overall structure and function of the protein it becomes part of.

The Twenty Core Amino Acids: A Diverse Toolkit

While many amino acids exist in nature, only twenty are commonly used in the genetic code to build proteins in living organisms. These are often referred to as the canonical or standard amino acids. Each of these twenty has a specific R group that contributes to the protein's final structure and function. They can be classified based on their R-group properties:

• Nonpolar, Aliphatic R Groups: These amino acids have hydrophobic side chains composed of hydrocarbons. They tend to cluster together within the interior of a protein, away from the aqueous environment. Examples include:
  • Alanine (Ala, A): A simple methyl group as its side chain.
  • Valine (Val, V): An isopropyl group.
  • Leucine (Leu, L): An isobutyl group.
  • Isoleucine (Ile, I): A sec-butyl group.
  • Glycine (Gly, G): Although technically not aliphatic, it's often grouped here. Glycine has a hydrogen atom as its side chain, making it the smallest amino acid. This small size allows it to fit into tight spaces within a protein structure and provides flexibility to the polypeptide chain.
  • Proline (Pro, P): Proline has a unique cyclic structure where its side chain is bonded to both the α-carbon and the nitrogen atom of the amino group. This creates a rigid ring that restricts the flexibility of the polypeptide chain and often disrupts regular secondary structures like alpha-helices.
• Aromatic R Groups: These amino acids contain aromatic rings in their side chains. They are relatively nonpolar and can participate in hydrophobic interactions. They also absorb ultraviolet light, which is useful for protein detection and quantification. Examples include:
  • Phenylalanine (Phe, F): Contains a benzyl group.
  • Tyrosine (Tyr, Y): Contains a phenol group (a hydroxyl group attached to a benzene ring). Tyrosine can also form hydrogen bonds due to the hydroxyl group.
  • Tryptophan (Trp, W): Contains an indole ring system. Tryptophan is the bulkiest amino acid and has the highest UV absorbance.
• Polar, Uncharged R Groups: These amino acids have side chains that are polar but uncharged at physiological pH. They can form hydrogen bonds with water and other molecules, making them more soluble in aqueous environments. Examples include:
  • Serine (Ser, S): Contains a hydroxyl group (-OH).
  • Threonine (Thr, T): Contains a hydroxyl group (-OH) and a methyl group.
  • Cysteine (Cys, C): Contains a sulfhydryl group (-SH), also known as a thiol group. Cysteine can form disulfide bonds (-S-S-) with other cysteine residues, which can stabilize protein structures.
  • Asparagine (Asn, N): The amide derivative of aspartic acid. Contains an amide group (-CONH2).
  • Glutamine (Gln, Q): The amide derivative of glutamic acid. Contains an amide group (-CONH2).
• Positively Charged (Basic) R Groups: These amino acids have side chains that are positively charged at physiological pH. They are hydrophilic and often found on the surface of proteins where they can interact with negatively charged molecules. Examples include:
  • Lysine (Lys, K): Contains an amino group (-NH3+) at the end of its side chain.
  • Arginine (Arg, R): Contains a guanidinium group, which is positively charged over a wide pH range.
  • Histidine (His, H): Contains an imidazole ring. Histidine's pKa is close to physiological pH, meaning it can be either protonated (positively charged) or deprotonated (neutral) depending on the local environment. This property makes histidine important in enzyme catalysis.
• Negatively Charged (Acidic) R Groups: These amino acids have side chains that are negatively charged at physiological pH. They are also hydrophilic and often found on the surface of proteins. Examples include:
  • Aspartic Acid (Asp, D): Contains a carboxyl group (-COOH) that is deprotonated to (-COO-) at physiological pH.
  • Glutamic Acid (Glu, E): Contains a carboxyl group (-COOH) that is deprotonated to (-COO-) at physiological pH.

The Peptide Bond: Linking Amino Acids Together

Amino acids are linked together by peptide bonds to form polypeptide chains. This is a dehydration reaction, meaning a water molecule is removed. The carboxyl group of one amino acid reacts with the amino group of another, forming a covalent bond between the carbon of the carboxyl group and the nitrogen of the amino group.

• Formation: The peptide bond is formed through a condensation reaction (also known as a dehydration reaction) where a molecule of water is eliminated. The carbon atom from the carboxyl group of one amino acid forms a covalent bond with the nitrogen atom from the amino group of another amino acid.
• Characteristics: The peptide bond has several important characteristics:
  • Planar: The peptide bond has partial double-bond character due to resonance, which makes it rigid and planar. This limits the conformational flexibility of the polypeptide chain.
  • Trans Configuration: The α-carbon atoms on either side of the peptide bond are typically in a trans configuration to minimize steric hindrance.
  • Polar: The peptide bond is polar, with the carbonyl oxygen carrying a partial negative charge and the amide nitrogen carrying a partial positive charge. This polarity allows the peptide bond to participate in hydrogen bonding.
• Polypeptide Chains: The sequential linking of amino acids through peptide bonds forms a polypeptide chain. The polypeptide chain has two distinct ends:
  • N-terminus: The amino end of the polypeptide chain, which contains a free amino group.
  • C-terminus: The carboxyl end of the polypeptide chain, which contains a free carboxyl group. The sequence of amino acids in a polypeptide chain is written from the N-terminus to the C-terminus, and this sequence is known as the primary structure of the protein.

Levels of Protein Structure: From Sequence to Function

The sequence of amino acids (primary structure) determines the higher levels of protein structure, ultimately dictating its function.

• Primary Structure: The primary structure is simply the linear sequence of amino acids in the polypeptide chain. It is determined by the genetic code and is unique for each protein. Even a single amino acid change in the primary structure can have significant consequences for the protein's function.
• Secondary Structure: The secondary structure refers to the local folding patterns of the polypeptide chain, stabilized by hydrogen bonds between the atoms of the peptide backbone. The two most common types of secondary structure are:
  • Alpha-helix: A coiled structure where the polypeptide backbone forms a helical shape, stabilized by hydrogen bonds between the carbonyl oxygen of one amino acid and the amide hydrogen of an amino acid four residues down the chain. The R groups point outward from the helix.
  • Beta-sheet: Formed by adjacent strands of the polypeptide chain aligned side-by-side, connected by hydrogen bonds between the carbonyl oxygen and amide hydrogen atoms. Beta-sheets can be parallel (strands run in the same direction) or antiparallel (strands run in opposite directions).
• Tertiary Structure: The tertiary structure is the overall three-dimensional shape of the protein, resulting from interactions between the R groups of the amino acids. These interactions include:
  • Hydrophobic interactions: Nonpolar R groups cluster together in the interior of the protein, away from water.
  • Hydrogen bonds: Form between polar R groups.
  • Ionic bonds: Form between oppositely charged R groups.
  • Disulfide bonds: Covalent bonds formed between the sulfhydryl groups of cysteine residues.
• Quaternary Structure: Some proteins are composed of multiple polypeptide chains, called subunits. The quaternary structure refers to the arrangement of these subunits in the protein complex. Subunits are held together by the same types of interactions that stabilize the tertiary structure. Not all proteins have quaternary structure; it is only present in proteins with multiple subunits.

Beyond the Twenty: Non-Standard Amino Acids

While the twenty standard amino acids are the primary building blocks, other amino acids exist and play crucial roles in specific proteins and biological processes. These are often referred to as non-standard or non-canonical amino acids.

• Modified Amino Acids: Some amino acids are modified after they have been incorporated into a polypeptide chain. These modifications can alter the amino acid's properties and influence protein function. Common modifications include:
  • Hydroxylation: The addition of a hydroxyl group (-OH) to proline or lysine. Hydroxyproline is important for the stability of collagen.
  • Phosphorylation: The addition of a phosphate group (-PO42-) to serine, threonine, or tyrosine. Phosphorylation is a key regulatory mechanism in cells, affecting protein activity and signaling pathways.
  • Glycosylation: The addition of a sugar molecule to asparagine, serine, or threonine. Glycosylation can affect protein folding, stability, and interactions with other molecules.
  • Carboxylation: The addition of a carboxyl group (-COOH) to glutamate. Carboxyglutamate is important for blood clotting.
• Selenocysteine: This is considered the "21st amino acid" and is incorporated into proteins during translation using a special tRNA and a specific mRNA codon (UGA, which usually signals a stop). Selenocysteine contains selenium instead of sulfur and is found in enzymes involved in antioxidant defense.
• Pyrrolysine: This is the "22nd amino acid" and is found in some archaea and bacteria. It is incorporated into proteins using a specific tRNA and mRNA codon (UAG, which usually signals a stop).

The Importance of Amino Acid Sequence

The precise sequence of amino acids in a protein is absolutely critical for its function. Even a single amino acid substitution can have dramatic consequences.

• Sickle Cell Anemia: A classic example of the importance of amino acid sequence is sickle cell anemia. This genetic disease is caused by a single amino acid change in the beta-globin chain of hemoglobin. In normal hemoglobin, the sixth amino acid is glutamic acid (a negatively charged amino acid). In sickle cell hemoglobin, glutamic acid is replaced by valine (a nonpolar amino acid). This seemingly small change causes the hemoglobin molecules to aggregate, distorting the shape of red blood cells into a sickle shape. These sickle-shaped cells are less flexible and can block small blood vessels, leading to pain, organ damage, and other complications.
• Enzyme Specificity: Enzymes are highly specific for their substrates, and this specificity is determined by the precise arrangement of amino acids in the enzyme's active site. The active site is the region of the enzyme that binds to the substrate and catalyzes the chemical reaction. The amino acids in the active site must be positioned correctly to interact with the substrate and facilitate the reaction.

Protein Synthesis: From Gene to Protein

The process of protein synthesis, also known as translation, involves decoding the genetic information encoded in mRNA to assemble a polypeptide chain.

• Transcription: The first step in protein synthesis is transcription, where the DNA sequence of a gene is copied into an mRNA molecule. This process occurs in the nucleus.
• Translation: The mRNA molecule then travels to the ribosomes in the cytoplasm. Ribosomes are complex molecular machines that facilitate the translation of the mRNA code into a polypeptide chain.
• tRNA: Transfer RNA (tRNA) molecules act as adaptors, bringing the correct amino acid to the ribosome based on the mRNA sequence. Each tRNA molecule has an anticodon that is complementary to a specific codon on the mRNA.
• Codons: The mRNA sequence is read in three-nucleotide units called codons. Each codon specifies a particular amino acid. There are 64 possible codons, but only 20 amino acids. This means that some amino acids are specified by multiple codons (redundancy). There are also start codons (typically AUG, which codes for methionine) and stop codons (UAA, UAG, UGA), which signal the beginning and end of the polypeptide chain.
• The Ribosome Cycle: The ribosome moves along the mRNA molecule, reading each codon and adding the corresponding amino acid to the growing polypeptide chain. This process continues until a stop codon is reached. The completed polypeptide chain is then released from the ribosome and folds into its proper three-dimensional structure.

Functions of Proteins: The Molecular Machines of Life

Proteins perform a vast array of functions in living organisms, making them essential for life. Some key functions include:

• Enzymes: Catalyzing biochemical reactions. Enzymes are biological catalysts that speed up chemical reactions in cells. They are highly specific for their substrates and can increase the rate of reactions by millions of times.
• Structural Proteins: Providing support and shape to cells and tissues. Examples include collagen (found in connective tissue), keratin (found in hair and nails), and actin and myosin (found in muscle).
• Transport Proteins: Carrying molecules across cell membranes or throughout the body. Examples include hemoglobin (carries oxygen in the blood), glucose transporters (transport glucose across cell membranes), and ion channels (allow ions to flow across cell membranes).
• Motor Proteins: Enabling movement. Motor proteins use energy from ATP to move along cellular tracks or filaments. Examples include kinesin and dynein (involved in intracellular transport) and myosin (involved in muscle contraction).
• Antibodies: Defending the body against foreign invaders. Antibodies are proteins produced by the immune system that recognize and bind to specific antigens (foreign molecules).
• Hormones: Coordinating communication between different parts of the body. Hormones are signaling molecules that are produced in one part of the body and travel through the bloodstream to reach target cells in other parts of the body.
• Receptor Proteins: Receiving and responding to signals from the environment. Receptor proteins bind to specific signaling molecules and trigger a cellular response.
• Storage Proteins: Storing nutrients. Examples include ferritin (stores iron) and casein (stores amino acids in milk).

Protein Folding and Misfolding: A Delicate Balance

The correct folding of a protein is essential for its function. However, protein folding is a complex process, and proteins can sometimes misfold.

• Chaperone Proteins: Chaperone proteins assist in protein folding and prevent aggregation. They bind to unfolded or misfolded proteins and help them to fold correctly.
• Protein Misfolding Diseases: Misfolded proteins can aggregate and form insoluble deposits, leading to a variety of diseases, including:
  • Alzheimer's disease: Characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain.
  • Parkinson's disease: Characterized by the accumulation of alpha-synuclein aggregates in the brain.
  • Huntington's disease: Caused by a mutation in the huntingtin gene, which leads to the production of a misfolded protein that aggregates in the brain.
  • Prion diseases: Caused by misfolded prion proteins that can convert normal prion proteins into the misfolded form. Examples include mad cow disease and Creutzfeldt-Jakob disease.

Conclusion: Amino Acids - The Foundation of Protein Function

In conclusion, proteins are intricate molecules built from the simpler organic compounds called amino acids. The sequence of these amino acids, dictated by our genes, determines the protein's unique three-dimensional structure and, ultimately, its function. Understanding the properties of amino acids, how they link together, and how proteins fold is fundamental to understanding the molecular basis of life and disease. From catalyzing biochemical reactions to providing structural support and transporting essential molecules, proteins are the indispensable workhorses of our cells, and their function hinges on the precise arrangement of their amino acid building blocks.