Membranes and Receptors Module - Proteins Overview

Membranes and Receptors Module - Session 1, Lecture 1.2 - Proteins of Cell Membrane

• The lecture is about proteins of cell membranes.
• The objectives include understanding the distribution and role of proteins in membrane structure, the importance of asymmetrical distribution of membrane proteins, and the structure of the erythrocyte cytoskeleton.

Lipid Mosaic Theory of Membrane Structure

• Biological membranes are composed of a lipid bilayer with associated proteins.
• Proteins can be peripheral or integral.
• Peripheral proteins are bound to the membrane surface by electrostatic and hydrogen bonds, and can be removed by changes in pH or ionic strength.
• Integral proteins are deeply embedded within the hydrophobic regions of the lipid bilayer, requiring detergents or organic solvents for removal.

Fluid Mosaic Model

• The model depicts the arrangement of phospholipids and proteins within the membrane structure.
• Integral proteins are depicted as traversing the lipid bilayer, while peripheral proteins are positioned on the membrane's surface.
• The model highlights the fluid nature of membranes, allowing for protein and lipid movement.

Importance of Asymmetrical Distribution of Membrane Proteins

• Asymmetrical protein orientation is crucial for membrane function.
• Examples: receptors for hydrophilic extracellular messengers (e.g., insulin) require their recognition sites to face the extracellular space.
• This precise arrangement allows for proper signal transduction and cellular response.

Erythrocyte Cytoskeleton

• The erythrocyte cytoskeleton provides structural support and maintains the cell's shape.
• It is a network of spectrin and actin molecules.
• Spectrin is a long, floppy rod-like molecule composed of alpha and beta subunits.
• These subunits form heterodimers that associate to create a heterotetramer (alpha2beta2).
• Spectrin-actin networks connect to the membrane through adapter proteins (ankyrin, band 4.1, adducin).

Composition of Red Blood Cell (RBC) Membrane

• RBC membranes are composed of:
  • 50% protein
  • 20% phospholipid
  • 20% cholesterol
  • 10% carbohydrate

Distinguishing Peripheral and Integral Proteins

• Peripheral proteins are released when ghost membranes are treated with high ionic strength media or pH changes.
• Integral proteins (e.g., bands 3 and 7) require detergents to dissociate from the membrane.
• Peripheral proteins are located on the cytoplasmic face of the membrane, as they are accessible to proteolysis there.

Glycoproteins and Membrane Stability

• Many membrane proteins are glycoproteins, possessing covalently linked carbohydrate units.
• Extracellular carbohydrate groups are highly hydrophilic, contributing to membrane stability by preventing flip-flop rotation of the proteins.
• These carbohydrate units also play a role in cellular recognition and immune reactions.

Haemolytic Anemias

• RBC cytoskeleton is essential for maintaining deformability during capillary passage without hemolysis.
• Hereditary spherocytosis involves reduced spectrin levels, resulting in spherocytes and premature erythrocyte destruction (hemolysis).
• Hereditary elliptocytosis involves spectrin abnormalities leading to fragile elliptoid cells.