Proteins: Structure, Function, and Classification

Posted on Dec 4, 2024 in Biology

Proteins

Proteins are organic biomolecules formed by carbon, oxygen, hydrogen, and nitrogen, and to a lesser extent, sulfur and phosphorus. Sometimes other elements such as iron and copper are also present. These complex macromolecules have high molecular weights and are formed by the union of simpler molecules called amino acids. In other words, proteins are polymers whose monomers are amino acids.

Amino Acids

Structure

Amino acids are the structural units of proteins. While about 200 different amino acids are known, only 20 are part of proteins. These are called protein amino acids and are the same in all living things.

Although different, all amino acids have in common:

  • A carboxyl group (-COOH)
  • An amino group (-NH2) bound to the alpha carbon (Cα), the carbon located next to the carboxyl carbon. These amino acids are called α-amino acids.
  • A hydrogen atom also bound to the Cα
  • A side chain (-R) of varying complexity, also bound to the Cα. This side chain differentiates the various amino acids.

Autotrophic organisms can synthesize all amino acids from inorganic compounds. Heterotrophs can only synthesize some amino acids from other organic compounds; the rest must be obtained from dietary protein. These amino acids that cannot be synthesized are called essential amino acids. Essential amino acids for humans include valine, leucine, isoleucine, methionine, phenylalanine, threonine, tryptophan, lysine, and histidine (also essential for children).

Amino acids are often referred to generically as “aa” and specifically by their full name or by a three-letter abbreviation, usually the first three letters of the name (e.g., leucine or Leu, valine or Val).

Properties

Amino acids are simple organic compounds of low molecular weight. They are solid, water-soluble, crystallizable, colorless, and have a high melting point (over 200°C). They exhibit stereoisomerism, optical activity, and amphoteric behavior.

  • Stereoisomerism: All amino acids except glycine possess an asymmetric carbon (Cα). This results in stereoisomerism, with each amino acid having two stereoisomers depending on the placement of the -NH2 group. If the -NH2 group is located to the right, it has a D-configuration; if to the left, an L-configuration. Amino acids that form proteins are all of the L-configuration.
  • Optical Activity: The presence of the asymmetric carbon also confers optical activity. In solution, they can rotate the plane of polarized light. If they rotate it to the right (+), they are called dextrorotatory; if to the left (-), levorotatory.
  • Chemical Behavior (Amphoteric): Amino acids are amphoteric substances, meaning they can behave as both acids and bases in aqueous solution depending on the pH. This is due to the presence of the acidic carboxyl group and the basic amino group.
    In aqueous solutions near neutral pH, amino acids are ionized, forming zwitterions (dipolar ions). The carboxyl group loses a proton (acting as an acid), and the amino group gains a proton (acting as a base). In some amino acids, side chains with amino and carboxyl groups are also ionized.
    If the pH decreases (acidic medium), the H+ concentration increases. The amino acid captures H+, becoming positively charged and behaving as a base.
    If the pH increases (basic medium), the H+ concentration decreases. The amino acid releases protons, becoming negatively charged and behaving as an acid.
    The pH at which the amino acid is in its neutral zwitterion form (equal number of positive and negative charges) is called the isoelectric point (pI).
    At pH > pI, the amino acid is negatively charged.
    At pH < pI, the amino acid is positively charged.

Classification

Amino acids are classified into several groups based on their side chains:

  1. Acidic Amino Acids: Negatively charged at pH 7. Side chains contain carboxyl groups. Examples: glutamic acid (Glu) and aspartic acid (Asp).
  2. Basic Amino Acids: Positively charged at pH 7. Side chains contain amino groups. Examples: lysine (Lys), histidine (His), and arginine (Arg).
  3. Neutral Amino Acids: No charge at pH 7. Side chains lack carboxyl or amino groups. Subdivided into:
    • Neutral Nonpolar: Hydrophobic side chains (hydrocarbon chains). Examples: alanine (Ala), valine (Val), leucine (Leu), isoleucine (Ile), proline (Pro), methionine (Met), phenylalanine (Phe), and tryptophan (Trp).
    • Neutral Polar: Hydrophilic side chains with uncharged polar groups like -OH, -NH2, -SH. Can form hydrogen bonds with water or other polar groups.

Peptide Bond

The peptide bond links amino acids to form peptides and proteins. It forms between the carboxyl group of one amino acid and the amino group of the next, releasing a water molecule. These bonds are broken by hydrolysis, splitting peptides and proteins into their constituent amino acids. This can be achieved chemically (acids, alkalis) or enzymatically (proteolytic enzymes).

Key characteristics of the peptide bond:

  • Covalent amide bond
  • Partial double bond character, restricting rotation between the atoms involved (C, N, O, and H lie in the same plane).
  • Rotation is possible around the bonds of the alpha carbon (Cα).
  • The oxygen of the carbonyl group and the hydrogen of the amino group have a trans configuration (opposite sides of the bond).

Peptides and Proteins

Peptides: Compounds composed of amino acids linked by peptide bonds. Can be obtained by partial hydrolysis of proteins. Some natural peptides (insulin, oxytocin) have important biological roles. Classified by amino acid number:

  • Oligopeptides: 2-10 amino acids (di-, tri-, tetra-peptides, etc.).
  • Polypeptides: More than 10 amino acids.

Proteins: Polypeptides with molecular weights greater than 5,000 amu. Some proteins consist of multiple polypeptide chains.

Protein Structure

Proteins are long-chain polypeptides (sometimes single chains) with a specific spatial configuration called the native conformation. Their function depends on this spatial arrangement. Protein structure is determined by four levels: primary, secondary, tertiary, and quaternary.

Primary Structure

The amino acid sequence of the protein. Determines which amino acids compose the chain and their order. Genetically determined and influences other structural levels. Any change in the sequence results in a different protein.

The peptide chain has a backbone of repeating units (-CH-CO-NH-) arranged in a zigzag pattern due to rotation around the Cα bonds. Amino acid side chains (R) extend alternately from either side of the backbone.

Each chain has an N-terminus (free amino group) and a C-terminus (free carboxyl group). Amino acids are numbered from the N-terminus to the C-terminus.

Secondary Structure

The spatial arrangement of the amino acid chain (primary structure) due to rotation around the Cα bonds. Two main types:

  • α-helix: Tight, clockwise spiral. Each turn contains 3.6 amino acids, with a distance of 5.4 Å between turns. Side chains project outwards. Stabilized by hydrogen bonds between NH and CO groups of different peptide bonds.
  • β-sheet (folded sheet): Parallel or antiparallel polypeptide segments arranged in a zigzag pattern. Stabilized by hydrogen bonds between NH and CO groups of adjacent segments. Side chains extend alternately above and below the sheet.

Tertiary Structure

The three-dimensional arrangement of the secondary structure. Determines the overall shape of the protein molecule (conformation). Maintained by various bonds between amino acid side chains:

  • Disulfide bridges (covalent bonds between cysteine residues)
  • Hydrogen bonds (between polar groups)
  • Electrostatic forces (between charged groups)
  • Van der Waals forces and hydrophobic interactions (between nonpolar groups)

Two main types:

  • Globular: Compact, roughly spherical shape. Soluble in water and salt solutions. Dynamic roles.
  • Fibrous: Elongated shape. Insoluble. Structural roles.

Quaternary Structure

Present only in proteins with multiple polypeptide chains (subunits or protomers). Describes how these subunits assemble to form the functional protein. Stabilized by similar bonds as the tertiary structure (between side chains of different subunits). Proteins with quaternary structure are called oligomeric (dimers, trimers, etc.).

Properties of Proteins

  • Chemical Behavior: Like amino acids, proteins are amphoteric, acting as buffers against pH changes.
  • Solubility: Depends on factors like pH, conformation, and residue arrangement. Fibrous proteins are insoluble, while globular proteins are soluble, forming colloidal dispersions. Solubility is influenced by surface residues and the solvation layer.
  • Specificity: Proteins are often species-specific, unlike lipids and carbohydrates. Specificity arises from the amino acid sequence. Important in immune responses and organ rejection.
  • Denaturation: Loss of native conformation and function due to environmental changes (temperature, pH, UV radiation). Disrupts secondary, tertiary, and quaternary structures, but not primary structure. Can be reversible (renaturation) or irreversible.

Classification of Proteins

Proteins are classified based on their composition:

  1. Simple Proteins (Holoproteins): Composed only of amino acids. Further classified by conformation:
    • Globular Proteins: Soluble, biologically active. Examples: albumins (serum albumin, egg albumin, lactoalbumin), globulins (serum globulins, ovoglobulins, lactoglobulin), protamines, and histones.
    • Fibrous Proteins: Insoluble, structural roles. Examples: collagens, elastin, keratins, actin, myosin, and fibrin.
  2. Conjugated Proteins (Heteroproteins): Contain a non-protein prosthetic group. Classified by the prosthetic group:
    • Chromoproteins: Colored prosthetic group (pigments). Examples: hemoglobin, myoglobin, cytochromes, hemocyanin, and rhodopsin.
    • Glycoproteins: Carbohydrate prosthetic group. Examples: gonadotrophs, immunoglobulins (antibodies), and mucoproteins.
    • Lipoproteins: Lipid prosthetic group. Involved in lipid transport. Examples: chylomicrons, VLDL, LDL, and HDL.
    • Phosphoproteins: Phosphoric acid prosthetic group. Examples: casein and vitellin.
    • Nucleoproteins: Nucleic acid prosthetic group. Examples: chromatin and chromosomes.

Protein Functions

  • Structural: Form cellular and extracellular structures (membranes, cytoskeleton, chromatin, tendons, cartilage, etc.).
  • Reserve: Store amino acids (ovalbumin, casein).
  • Homeostatic: Maintain internal environment (osmotic balance, buffering).
  • Transport: Carry molecules (permeases, hemoglobin, hemocyanin, myoglobin, cytochromes, lipoproteins, serum albumin).
  • Defensive: Protect the organism (thrombin, fibrinogen, mucins, immunoglobulins).
  • Hormonal: Regulate metabolic processes (insulin, glucagon, parathyroid hormone).
  • Contractile: Enable movement (actin, myosin, dynein).
  • Catalytic: Catalyze biochemical reactions (enzymes).