Proteins 3

Cellular Biology & Homeostasis

Amino Acids & Proteins

• Focus on protein structure and function.

Learning Objectives

• Understanding Protein Structure: Describe the various structures of proteins (primary, secondary, tertiary, quaternary).

• Protein Folding: Explain the relevance of protein folding.

• Chaperone Molecules: Understand the function of chaperone molecules in protein folding.

• Protein Denaturation: Describe what protein denaturation is and its implications.

• Classification of Proteins: Understand how proteins can be classified with examples.

Protein Structure

Types of Structures

• Primary Structure

  • Sequence of amino acids in a polypeptide chain linked by peptide bonds.

  • Peptide bonds are strong, covalent, and resistant to denaturation methods.

  • This sequence determines the higher levels of protein structure and ultimately, its function.

• Secondary Structure

  • Includes arrangements like α-Helix, β-Sheet, β-Bends.

  • Stabilized by hydrogen bonds between amino acids.

  • Side chains extend outward to avoid interference

    • α-Helix: A right-handed coil stabilized by hydrogen bonds, commonly found in fibrous proteins.

      • α-Keratins - rigidity determined by # of disulfide bridges between helices

    • β-Sheet: Composed of parallel or antiparallel strands, also stabilized by hydrogen bonds, important for the structural integrity of many proteins.

      • Anti-parallel more stable

      • Typically 3-10 AA long

      • ex. Fibroin - spider/moth silk

    • β-Bends: Irregular structures that connect two segments of anti-parallel β-sheets, helps change direction.

      • Important for globular proteins

      • Typically 4 AA, one is often proline

• Tertiary Structure

  • Three-dimensional arrangement of a single polypeptide chain.

  • Comprised of one or more protein secondary structures.

  • Hydrophobic interactions, ionic bonds, hydrogen bonds, and disulfide bridges between cysteines.

• Quaternary Structure

  • Refers to the assembly of two or more polypeptide chains (subunits) into a functional protein complex. Each subunit retains its own primary, secondary, and tertiary structures.

  • Held together by non-covalent interactions - H bonds, ionic bonds, hydrophobic interactions

  • Hemoglobin is a key example, consisting of four subunits that work together for efficient oxygen transport in the blood.

Protein Folding

• Proteins typically require assistance from chaperones for proper folding, quality control.

• Misfolded proteins can lead to pathologies such as Alzheimer's disease and cystic fibrosis.

• Chaperone proteins or Heat-Shock proteins (like Hsp70) help refold damaged proteins and prevent aggregation.

• Cycle -

  • Chaperone bound to ADP

  • Complex has high affinity for misfolded protein

  • Bind, ADP released

  • ATP binds, protein folds and then is released

Protein Denaturation

• Denaturation refers to the unfolding of proteins, affecting secondary and tertiary structures.

• Primary structure generally remains intact.

• Common denaturing agents include heat, strong acids/bases, detergents and heavy metal ions.

Classification of Proteins

Based on Structure

• Fibrous Proteins

  • Tough and strong, linear structures (e.g., collagen, keratin).

  • Structural functions

  • Insoluble in water

  • Secondary structure most important

• Globular Proteins

  • Spherical shapes, tightly packed

  • Mainly enzymes, antibodies, and some hormones (e.g., hemoglobin, insulin).

  • Physically softer

  • Soluble in water

  • Tertiary structure most important

• Intermediate Proteins

  • Mostly linear but exhibit a mix of fibrous and globular characteristics.

  • Soluble in water

  • Blood clotting

Based on Composition

• Simple Proteins

  • Composed solely of amino acids, simple (e.g., myosin, collagen).

• Conjugated Proteins

  • Contain non-amino acid components (prosthetic groups) essential for function (e.g., glycoproteins, lipoproteins).

  • Usually globular/soluble

  • Types:

    • Phosphoproteins - phosphoric acid (casein/milk, vitellin/egg)

    • Glycoproteins - carbohydrate (membrane ptns)

    • Nucleoproteins - nucleic acid (ptns in chromosomes/ribosomes)

    • Chromoproteins - pigment (heme)

    • Lipoproteins - lipid (chylomicrons)

    • Flavoproteins - FAD (ETC)

    • Metalloproteins - metal ions (hemocyanin in HS crabs)

Based on Function

• Structural Proteins: Provide support (e.g., collagen).

• Enzymes: Catalysts for biochemical reactions (e.g., DNA polymerase).

• Hormones: Regulate physiological processes (e.g., insulin).

• Transport Proteins: Assist in molecular transport (e.g., albumin).

• Contractile Proteins: Involved in muscle contraction (e.g., actin, myosin).

• Storage Proteins: Store nutrients (e.g., ferritin).

• Toxins: Harmful proteins (e.g., snake venom).