9-Proteins: Structure, Function, and Clinical Relevance in Cell Biology

Proteins: An Overview

Introduction to Proteins

Proteins are essential biomolecules that perform a vast array of functions within living cells. They are involved in structural support, catalysis, transport, signaling, and defense. The unique sequence and structure of each protein are determined by genetic information stored in DNA.

• Proteins execute the fundamental tasks of every living cell.

• The process of reading DNA information and synthesizing proteins is called translation.

• The amino acid sequence of a protein is coded for by DNA and is unique for each kind of protein.

Amino Acids: Building Blocks of Proteins

Structure and Classification of Amino Acids

Amino acids are organic molecules that serve as the monomers of proteins. Each amino acid contains an amino group, a carboxyl group, a hydrogen atom, and a distinctive side chain (R group) attached to a central carbon atom.

• All amino acids have:

  • Two functional groups: an amino group (-NH2) and a carboxyl group (-COOH)

  • A hydrogen atom

  • A side chain (R group) that varies among amino acids

• There are approximately 20 different amino acids in living organisms.

• At the atomic level, proteins are composed of carbon, hydrogen, oxygen, nitrogen, and sometimes sulfur.

Essential vs. Non-Essential Amino Acids

Essential Amino Acids (from nutrition)	Non-Essential Amino Acids (synthesized by body)
Leucine Isoleucine Valine Histidine Lysine Methionine Phenylalanine Threonine Tryptophan	Alanine Arginine Asparagine Aspartic Acid Cysteine Glutamine Glutamic Acid Glycine Proline Serine Tyrosine

Classification by Side Chain Properties

• Acidic: Aspartic acid, Glutamic acid

• Basic: Lysine, Arginine, Histidine

• Neutral, Nonpolar: Tryptophan, Phenylalanine, Cysteine, Alanine, Valine, Isoleucine, Leucine, Methionine, Proline

• Neutral, Polar: Tyrosine, Serine, Threonine, Asparagine, Glutamine

Formation of Polypeptides

Peptide Bonds and Polypeptide Chains

Amino acids are linked together by peptide bonds to form polypeptide chains, which fold into functional proteins. The size of proteins is measured in Daltons (Da), with one amino acid averaging about 110 Da.

• Peptide Link: The chemical bond formed between the carboxyl group of one amino acid and the amino group of another.

• Polypeptides are long, unbranched chains of amino acids.

Types of Bonds in Polypeptides

• Peptide Bonds: Primary linkage in all protein structures.

• Disulfide Bridges: Covalent bonds between sulfur atoms of cysteine residues, stabilizing protein structure.

• Hydrogen Bonds: Weak bonds that stabilize secondary and tertiary structures.

Levels of Protein Structure

Primary Structure

The primary structure of a protein is its unique sequence of amino acids, linked by peptide bonds.

• Determined by the genetic code in DNA.

• Linear arrangement of amino acids.

Secondary Structure

Secondary structure refers to local folding patterns within a polypeptide, stabilized by hydrogen bonds.

• Alpha Helix: Coiled structure stabilized by hydrogen bonds every fourth amino acid.

• Beta Pleated Sheet: Sheet-like arrangement formed by hydrogen bonding between segments of the polypeptide chain.

• A single polypeptide may contain both types of secondary structure.

Tertiary Structure

Tertiary structure is the overall three-dimensional shape of a polypeptide, resulting from interactions among side chains.

• Stabilized by hydrogen bonds, ionic bonds, and disulfide bridges.

• Secondary structures are bent and folded into a complex 3D arrangement.

Quaternary Structure

Quaternary structure arises when two or more polypeptide chains (subunits) interact to form a functional protein complex.

• Examples: Collagen (three polypeptide chains), Haemoglobin (four polypeptide chains).

• Globular in shape, often found in aqueous environments.

Protein Folding, Stability, and Misfolding

Factors Influencing Protein Folding

Protein folding is influenced by various interactions, including hydrogen bonds, ionic bonds, hydrophobic interactions, and disulfide bridges. Proper folding is essential for biological activity.

• Environmental factors such as pH, temperature, and chemicals can disrupt folding.

• Disruption leads to denaturation, loss of structure and function.

Denaturation and Renaturation

Denaturation results in the disruption of secondary, tertiary, or quaternary structure, often leading to loss of biological activity. Renaturation may occur if the denaturing agent is removed and the protein refolds correctly.

• Caused by changes in pH, temperature, or exposure to chemicals.

• Example: Cooking an egg denatures egg proteins.

Protein Misfolding and Disease

Misfolded proteins can cause diseases, such as prion diseases, which are rare degenerative brain disorders in mammals.

• Prions: Infectious protein particles lacking nucleic acid, responsible for diseases like bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease (CJD).

• Prion diseases may be genetic, infectious, or sporadic.

• Misfolded prion protein (PrP) is the causative agent.

Protein Functions in Cells

Major Functions and Examples

Function	Example
Structure	Collagen in skin; keratin in hair, nails, horns
Movement	Actin and myosin in muscle
Defense	Antibodies in bloodstream
Storage	Albumin in egg white
Signaling	Growth hormone in bloodstream
Catalyzing reactions	Enzymes (e.g., amylase digests carbohydrates; ATP synthase makes ATP)
Blood Clotting	Fibrinogen, Fibrin
Transport	Haemoglobin

Classification of Proteins

• Fibrous Proteins: Provide structural support (collagen, elastin, keratin), contractile function (actin, myosin).

• Globular Proteins: Storage (ovalbumin, casein), transport (haemoglobin), cell signaling (hormones, receptors, enzymes), immune response (antibodies).

Function of Physiologically Active Proteins

• Depends on the ability to recognize and bind to other molecules.

• Examples:

  • Hormonal proteins bind to cell receptors.

  • Antibodies bind to foreign bodies.

  • Enzymes bind to substrates.

Clinical Relevance: Protein Deficiency and Excess

Protein Deficiency

• Leads to growth failure and diseases such as Kwashiorkor (characterized by edema and fatty liver).

• Collagen-related diseases:

  • Scurvy: Vitamin C deficiency impairs collagen folding.

  • Brittle bone disease: Defect in type I collagen gene affects bone formation.

Protein Excess

• May cause kidney stress (kidney stones).

• Can lead to nutritional deficiencies, bad breath, headache, and constipation due to insufficient fiber.

Summary Table: Protein Structure Levels

Level	Description	Bonds Involved
Primary	Sequence of amino acids	Peptide bonds
Secondary	Local folding (alpha helix, beta sheet)	Hydrogen bonds
Tertiary	3D folding of polypeptide	Hydrogen, ionic, disulfide bridges
Quaternary	Assembly of multiple polypeptides	Interactions among subunits

Key Equations

• Dalton (Da): $1~Da = 1~g/mol$

• Average amino acid mass: $\text{Amino acid} \approx 110~Da$

Additional info:

• Protein structure and function are central to cell biology, impacting cellular processes, health, and disease.

• Understanding protein folding and misfolding is crucial for biomedical research and therapeutic development.