Membrane Proteins: Integral and Peripheral

Membrane Proteins Overview - Gatekeepers & Signalers

• Proteins associated with the lipid bilayer; crucial for cell function.
• Roles: Act as channels, transporters (gatekeepers), receptors (signalers), enzymes, and cell adhesion molecules.
• Mediate interaction between cell and its environment.
• Structurally diverse, reflecting their varied functions.
• Essential for maintaining cellular homeostasis and communication.

⭐ Membrane proteins constitute about 50% of the mass of most plasma membranes, highlighting their functional importance (e.g., RBC membrane proteins like Spectrin, Ankyrin, Band 3, Glycophorin).

Integral Membrane Proteins - Deep Divers

• Embedded within or span lipid bilayer; hydrophobic regions ($\alpha$-helices, $\beta$-barrels) interact with lipid tails.
• Require strong detergents (e.g., SDS, Triton X-100) or organic solvents for extraction, disrupting membrane integrity.
• Major Types:
  • Transmembrane Proteins: Span the entire membrane.
    • Single-pass: Cross membrane once (e.g., Glycophorin A in RBCs, LDL receptor).
    • Multi-pass: Cross membrane multiple times (e.g., GPCRs - 7 helices, Band 3 protein, Rhodopsin, ion channels).
  • Partially Embedded Proteins: Do not span bilayer; anchored within one leaflet.
• Key Functions: Act as channels (e.g., Na+/K+ ATPase), transporters (e.g., GLUTs), receptors (e.g., insulin receptor, GPCRs), enzymes, and cell adhesion molecules.

⭐ G-protein coupled receptors (GPCRs) are the most extensive family of integral membrane proteins, characterized by 7 transmembrane $\alpha$-helices, and are the target for approximately 30-50% of all pharmaceutical drugs.

Peripheral Membrane Proteins - Surface Associates

• Bind to membrane surfaces or integral proteins via non-covalent interactions.
  • Primarily electrostatic forces and hydrogen bonds.
  • Do not span the hydrophobic core of the lipid bilayer.
• Solubilization:
  • Easily dissociated by mild treatments.
  • Examples: High ionic strength solutions (e.g., $ \textbf{1 M} \text{ NaCl} $), changes in pH, or addition of chelating agents like EDTA.
  • Detergents are not required for their removal.
• Key Functions & Examples:
  • Cytoskeletal components: Spectrin, Ankyrin (RBC membrane integrity).
  • Electron carriers: Cytochrome c (mitochondrial inner membrane).
  • Enzymes: Phospholipase A2.
  • Signal transduction proteins.

⭐ Defects in Spectrin or Ankyrin, key peripheral proteins, can lead to hereditary spherocytosis, causing fragile, sphere-shaped red blood cells and anemia.

IMP vs PMP Showdown - Key Distinctions

High‑Yield Points - ⚡ Biggest Takeaways

• Integral proteins: Embedded in bilayer; need detergents for extraction (e.g., Glycophorin, Band 3).
• Peripheral proteins: Loosely bound to surface; extracted by salt/pH changes (e.g., Spectrin, Ankyrin).
• Transmembrane domains: Often α-helices (GPCRs) or β-barrels (Porins).
• RBC cytoskeleton: Spectrin-Ankyrin (peripheral) crucial for cell shape and integrity.
• Lipid-anchored proteins: Covalently linked to lipids, anchoring them to the membrane.
• Fluid Mosaic Model: Proteins exhibit lateral mobility in a fluid lipid sea.