CHE414 Lecture 21 (Membranes and Membrane Proteins; F24)

Lecture Overview

• Lecture 21: Membranes and Membrane Proteins

• Topics: Membrane fluidity, composition, membrane proteins, transport mechanisms.

• Important upcoming items: Prelab, lab report, and quiz.

Membrane Fluidity

• Membrane fluidity is essential for proper function across temperature variations.

• Cholesterol's Role:

  • Rigid and planar structure decreases fluidity at high temperatures by stabilizing the membrane.

  • At low temperatures, cholesterol increases fluidity by preventing close packing of lipids.

Asymmetry of Biological Membranes

• Natural bilayers are asymmetric with distinct lipid compositions in each leaflet.

  • Leaflet 1 vs. Leaflet 2:

    • Leaflet 1 often faces the extracellular space; features lipids with carbohydrate groups.

    • Phosphatidylcholine is typically on the outer leaflet; phosphatidylserine remains on the interior.

Diffusion in Membranes

• Diffusion Types:

  • Transverse Diffusion: Very slow, maintaining distinct compositions on each side.

  • Lateral Diffusion: Much faster; lipids can switch places 10^7 times per second.

• Membrane transport proteins facilitate movement:

  • Flippases: Move lipids from one leaflet to another.

  • Floppases: Move lipids from cytosolic to exoplasmic side.

  • Scramblase: Bidirectional lipid flipping.

Composition of Membranes

• Biological membranes comprise both lipids and proteins; roughly 50% protein by weight on average.

• Comparisons of Membrane Compositions:

  • Red Blood Cell Membrane: 43% lipid, 57% protein.

  • Myelin Sheath: 79% lipid, 21% protein.

  • Variations exist based on membrane types (e.g., mitochondrial membranes).

Types of Membrane Proteins

• Integral Proteins (Transmembrane):

  • Span lipid bilayer, hydrophobic interior, hydrophilic exterior.

  • Released by detergents.

• Peripheral Proteins:

  • Loosely associated, often with one side, involving charge interactions or hydrogen bonding.

  • Easily removed by changing salt concentrations.

• Lipid-anchored Proteins:

  • Covalently attached lipid tethers protein.

Protein Structure and Interaction with Membranes

• Alpha Helices:

  • Composed of hydrophobic residues, intertwine with lipid acyl chains.

  • Polar backbone enriched with Ile, Leu, Val, Phe residues allows stability.

• Integral Membrane Proteins:

  • Common structures:

    • Helix Bundles: Comprising 20 amino acids each.

    • Beta Barrels: Minimum of 8 strands, creating a central cavity for passage.

Membrane Protein Anchoring

• Types of Lipid Modifications:

  • Myristoylation, Palmitoylation, Prenylation:

    • Attach lipid group to a protein side chain using amide or ester bonds.

• Lipids inserted into the cytoplasmic leaflet secure proteins within membranes.

The Fluid Mosaic Model

• Describes membranes as dynamic structures with proteins and lipids that move laterally but do not transversely cross freely (with some exceptions).

Membrane Transport

• Transport Mechanisms:

  • Simple Diffusion:

    • No energy or protein required; driven by concentration gradients.

Thermodynamics of Transport

• Transport can be described thermodynamically:

• ΔGexpression:

  • ΔGtransport = RT ln ([Ain]/[Aout])

  • Negative ΔG indicates spontaneous movement into the cell; positive ΔG indicates no spontaneous flow without energy.

Types of Mediated Transport

• Passive Transport (Facilitated Diffusion):

  • Molecules move from high to low concentration through specific carriers.

• Active Transport:

  • Molecules move against concentration gradients, requires energy.

Specialized Transport Proteins

• Porins:

  • Found in bacterial and mitochondrial membranes; allow passive transport of small molecules via β-barrel structures.

• Ion Channels:

  • More selective than porins; facilitate the transport of ions (example: K+ channel).

  • K+ channels show high selectivity based on pore structure and interaction with ion sizes.

Aquaporins and Water Transport

• Aquaporins facilitate rapid, specific water transport beyond simple diffusion.

• Example: AQP1 has a unique structure allowing efficient transport with strict selectivity for water.

Proton Jumping in Aquaporins

• Mechanism involves asparagine residues binding to water, disrupting hydrogen bond chains to ensure selective transport.

Conclusion

• Membranes are complex, dynamic structures important for cell integrity and function.