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Chapter 12: Membrane Structure/Function

Chapter 12: Membrane Structure/Function. The fibroblast membrane is a dynamic irregular structure; nuclei are stained blue and actin fibers yellow. Membranes contain between 18% and 75% protein content. Phospholipids and Glycolipids Self-Assemble to Form a Lipid Bilayer. Driving Forces :

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Chapter 12: Membrane Structure/Function

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  1. Chapter 12: Membrane Structure/Function The fibroblast membrane is a dynamic irregular structure; nuclei are stained blue and actin fibers yellow Membranes contain between 18% and 75% protein content.

  2. Phospholipids and Glycolipids Self-Assemble to Form a Lipid Bilayer • Driving Forces: • H-bonding • Hydrophobic effect • Electrostatic interactions • Van der Waal’s attractions (close packing)

  3. Membrane Fluidity: Temperature, Cholesterol and Fatty-Acid-Composition Regulated How does membrane composition alter with elevated temperature?

  4. Significant Lateral Albeit Minimal Transverse Lipid Movement Fluorescence recovery after photobleaching (FRAP) is a technique that allows the measurement of lateral mobility of membrane components.

  5. Liposome for Potential Drug Delivery Lipid shape drives overall structure: Wedge micelle bead Cylinder bilayer vesicle

  6. The ability of small molecules to cross a membrane is a function of its hydrophobicity. Indole is more soluble than tryptophan in membranes because it is uncharged. Ions cannot cross membranes because of the energy cost of shedding their associated water molecules.

  7. Is observed permeability across a membrane expected? reasonable? justifiable?

  8. Peripheral and Integral Proteins Different membrane orientation (a and e), surface position (f and e) and membrane componentassociation (d and e) What tethers peripheral proteins to the membrane? What secondary structure is common in membrane hydrophobic regions?

  9. Hydropathy Plots Identify Potential Trans-Membrane Peptide Regions Hydrophobicity Index: the free energy needed to transfer successive segments of a polypeptide from a non-polar solvent to water Hydropathy Plot

  10. Integral membrane proteins: embedded in the hydrocarbon core of the membrane. Peripheral membrane proteins: bound to the polar head groups of membrane lipids or to integral membrane proteins. Attachment? Some proteins are associated with membranes by attachment to a hydrophobic moiety that is inserted into the membrane. Attachment?

  11. Alpha Helices Compose the Integral Protein Bacteriorhodopsin Bacteria light-harvesting protein that generates proton gradient α-Helix most common 2° membrane structure Helical (yellow) and charged (red)residues

  12. Bacterial Channel - Porin Beta barrel with a hydrophobic exterior and a hydrophilic core Hydrophobic (yellow) and hydrophobic (white) residues shown

  13. Partially-Embedded Prostaglandin Synthase Converts arachi-donic acid (20:4) to prostaglandin H2

  14. Aspirin Blocks Prostaglandin Synthase Hydrophobic Channel Prostaglandin stimulates inflammation responses and reduces gastric acid secretion

  15. Sodium Gradient Formed via a Na+-K+ATPaseAntiport Pump • P-type ATPases form a phosphorylaspartate and include: • Ca+2ATPases for muscle contraction • Gastric H+-K+ATPases Link http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__how_the_sodium_potassium_pump_works.html

  16. Secondary Transport via a Common Sodium Concentration Gradient • Na+-K+ATPaseantiporter gradient drives: • Glucose import via a Na+- glucose symporter • Calcium ion export • via a Na+-Ca+2 • antiporter

  17. Digoxin Na+-K+ Pump Inhibition Reduces Ca+2 Transport Digoxin – a cardiotonic steroid medication used for atrial fluttering and heart failure. How can digoxin be chemically described? Digitalis purpurea

  18. Motor Protein Actin interacts with the thick filament of myosin causing muscle contraction Thick Filament

  19. Myosin Head and Neck Region

  20. Myosin-Actin Reaction Cycle

  21. Ca+2 Allows for Myosin-Actin Binding Actin How does digoxin affect muscle contraction? Actin

  22. Digoxin Na+-K+ Pump Inhibition via Dephosphorylation Blocking Calcium ion export via a Na+-Ca+2antiporter How does digoxin affect Ca+2 abundance? Digitalis purpurea

  23. Size Selective Channel Only Allows Potassium Ion Passage • K+ movement: • Down the concentration gradient • From cytosol to cell exterior Cell exterior Cytosol

  24. Selectivity Filter Determines the Preference of K+ Over Other Ions Two of four trans-membrane alpha helices shown Dehydrated K+ ions move across the membrane Ionic diameter K+ = 2.66 Å and Na+ = 1.9 Å Why does Na+ not move through this pore?

  25. Energetic Basis of Ion Selectivity K+ energy balance: Dehydration versus Carbonyl oxygen resolvation in selectivity-filter lining Does tight K+ binding slow transport across the channel?

  26. Electrostatic Repulsion Forces Pushes and Speeds K+ Through Ion Channel • Selectivity filter contains 4 binding sites • Ions move down the concentration gradient

  27. Na+ Channel Blocker Specific in blocking Na+ while having no effect on K+ Reversible binding: hydrated Na+ (nsec), tetrodotoxin (0.3 min) Lethal dose in humans: 10 ng Pufferfish: a Japanese delicacy and highly toxic How does this cork-like toxin position itself? Host-toxicity prevention mechanism?

  28. Chapter 12 Problems: 1-10, 12-15

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