Essential Cell Biology: Protein Structure and Function

Essential Cell Biology: Chapter 4 - Protein Structure and Function

Overview of Proteins

  • Definition: Proteins are the main building blocks from which cells are assembled.

  • Composition: Constitute most of the cell's dry mass.

  • Functions: Provide cell shape and structure, execute cellular functions; structurally complex and functionally sophisticated molecules.

Types of Proteins and Their Functions

  • Enzymes

    • Function: Catalyze covalent bond breakage or formation.

    • Examples:

    • Alcohol dehydrogenase (makes alcohol in wine).

    • Pepsin (degrades dietary proteins in the stomach).

    • Ribulose-1,5-bisphosphate carboxylase/oxygenase (converts CO2 to sugars in plants).

    • DNA polymerase (copies DNA).

    • Protein kinase (adds a phosphate group to proteins).

  • Structural Proteins

    • Function: Provide mechanical support to cells and tissues.

    • Examples:

    • Collagen (extracellular fibers in tendons and ligaments).

    • Tubulin (forms microtubules).

    • Actin (forms support filaments beneath plasma membrane).

    • Keratin (major protein in hair and horns).

  • Storage Proteins

    • Function: Store amino acids or ions.

    • Examples:

    • Ferritin (stores iron in the liver).

    • Ovalbumin (source of amino acids for developing bird embryos).

    • Casein (source of amino acids for baby mammals).

  • Signal Proteins

    • Function: Carry extracellular signals from cell to cell.

    • Examples:

    • Insulin (controls blood glucose levels).

    • Netrin (guides nerve cell axons).

    • Nerve Growth Factor (stimulates nerve cells to grow).

    • Epidermal Growth Factor (stimulates epithelial cell growth).

  • Receptor Proteins

    • Function: Detect signals and transmit them to the cell's response machinery.

    • Examples:

    • Rhodopsin (detects light).

    • Acetylcholine receptor (activated by acetylcholine).

    • Insulin receptor (enables glucose uptake).

    • Adrenergic receptor (increases heartbeat rate).

  • Special-purpose Proteins

    • Function: Highly variable roles.

    • Examples:

    • Antifreeze proteins (prevent blood freezing in Arctic fishes).

    • Green fluorescent protein (emits light).

    • Monellin (intensely sweet protein from an African plant).

    • Glue proteins from mussels (allow attachment to surfaces in seawater).

  • Transport Proteins

    • Function: Carry small molecules or ions.

    • Examples:

    • Serum albumin (carries lipids in bloodstream).

    • Hemoglobin (transports oxygen).

    • Transferrin (carries iron).

    • Glucose transporters (shuttle glucose across membranes).

    • Ca²+ pumps (remove Ca²+ from muscle cytosol).

  • Motor Proteins

    • Function: Generate movement in cells and tissues.

    • Examples:

    • Myosin (contracts skeletal muscles).

    • Kinesin (moves organelles).

    • Dynein (helps cilia and flagella movement).

  • Transcription Regulators

    • Function: Bind to DNA to switch genes on or off.

    • Examples:

    • Lac repressor (silences lactose-degrading enzymes in bacteria).

    • Various DNA-binding proteins (control development).

Protein Structure

  • Definition: A protein is made from a long chain of amino acids held by covalent peptide bonds.

  • Amino Acids: Proteins are assembled from 20 different amino acids with unique properties.

  • Polypeptides: Another term used for proteins; the unique order of amino acids in a polypeptide chain is called the amino acid sequence.

  • Amino Acid Sequence: Same for every molecule of a particular protein (e.g., all human insulin molecules have the same sequence).

Polypeptide Structure

  • Backbone Composition:

    • Formed from a sequence of core atoms (–N–C–C–).

    • Ends of each amino acid include:

    • Amino terminus (N-terminus): Contains amino group (NH3 +).

    • Carboxyl terminus (C-terminus): Contains carboxyl group (COO–).

  • Side Chains: Project from the backbone; define the unique chemical properties of each amino acid (interaction with the environment).

Protein Folding and Noncovalent Bonds

  • Flexibility of Chains: Long polypeptide chains can fold in many ways because of bond rotation.

  • **Noncovalent Bonds Types:

    • Hydrogen bonds: Made between polar atoms in the polypeptide backbone and side chains.

    • Ionic bonds: Involve charged side chains.

    • Van der Waals interactions: Provide marginal attraction between closely positioned atoms.

  • Hydrophobic Forces:

    • Definition: Nonpolar side chains tend to cluster inside the folded protein in aqueous environments to minimize disruptive interactions with water.

  • Hydrogen Bonds:

    • Stabilize folded protein shape by linking polar side chains or backbone to maintain internal structure.

Protein Diversity

  • Range of Protein Sizes: Proteins vary from about 30 to over 10,000 amino acids, with most being between 50 and 2000.

  • Types of Protein Shapes: Proteins can be globular or fibrous, forming structures like filaments, sheets, rings, or spheres.

Protein Models

  • Representation Models:

    • Backbone Model: Shows polypeptide organization.

    • Ribbon Model: Highlights the folding patterns of the polypeptide.

    • Wire Model: Includes amino acid positions, useful in predicting activities.

    • Space-filling Model: Displays the protein surface contour, revealing accessible amino acids.

Protein Folding and Stability

  • Denaturation and Renaturation:

    • A protein can be unfolded (denatured) using solvents disrupting noncovalent interactions.

    • When denaturing agents are removed, proteins can refold (renature) to their original shape, indicating that folding information is contained in the amino acid sequence.

  • Chaperone Proteins: Assist in protein folding by binding to partly folded chains or providing isolation chambers to prevent aggregation.

Secondary Structures: Alpha Helices and Beta Sheets

  • Alpha Helix:

    • Structure formed when a single polypeptide spins to form a cylinder with hydrogen bonds every fourth amino acid, yielding a right-handed helical shape.

    • Most common in transmembrane proteins, which protect hydrophilic backbones from membranes' hydrophobic environments.

  • Coiled-Coil Structure:

    • Formed by two or three alpha helices wrapping around each other maintaining their hydrophobic sides inward to minimize contact with water.

  • Beta Sheets:

    • Created by hydrogen bonds between adjacent polypeptide segments.

    • Types: Parallel (same orientation) and Antiparallel (opposite orientations).

  • Amyloid Structures: Beta sheets can stack to form structures with interdigitated side chains, significant in diseases like Alzheimer's due to misfolding.

Protein Assembly and Quaternary Structure

  • Binding Sites: Regions on protein surfaces that interact with other molecules via noncovalent bonds, allowing proteins to form larger structures.

  • Subunits: Each polypeptide chain in a protein with quaternary structure is called a subunit; proteins can have multiple identical or different subunits.

  • Hemoglobin Example: Contains two α-globin and two β-globin subunits arranged symmetrically.

  • Cross-linkages: Extracellular proteins are often stabilized by covalent cross-links (e.g., disulfide bonds between cysteine side chains), aiding structure maintenance under harsh conditions.

Special Proteins: Elastin and Cross-linkages

  • Elastin: Forms elastic fibers in tissues, allowing for stretching and recoiling; cross-linked into a meshwork structure contributing to elasticity.

Levels of Protein Organization

  • Primary Structure: Amino acid sequence of the polypeptide chain.

  • Secondary Structure: Includes alpha helices and beta sheets formed within certain segments.

  • Tertiary Structure: Entire three-dimensional conformation, including all loops and folds.

  • Quaternary Structure: Complex of multiple polypeptide chains interacting as a functional protein unit.