Membrane GUTS Lecture

1. Membrane GUTS Lecture Ken Jacobson Frap@med.unc.edu

2. Membranes are planar structures consisting primarily of lipids and proteins. • Membranes carry out a variety of fundamental roles for cells. • The organization of living systems depends very strongly on their ability to compartmentalize. Membranes define physical compartments into which only certain molecules can enter or leave. Thus, membranes provide a selective permeability barrier. • (2) Membranes provide molecular receptors (often proteins) by which compartments receive external signals. • (3) Cell-cell communication is often mediated by cell membranes (e.g., immune system, cellular assemblies). Communication can occur both through direct cell-cell contact and through soluble mediators.

3. (4) Membranes provide a support and regulation for enzymatic reactions (e.g., signal transduction in the immune system). (5) Some membranes provide a support for the generation and propagation of electrical signals (e.g., nerve impulse transmission and neuromuscular control). (5) Membranes are involved in energy conversion processes (e.g., the generation of ATP).

5. Membrane bounded organelles in the cell

7. The lipid bilayer

8. The bilayer is fluid!

9. Lipid bilayer fluidity • Temperature increases fluidity • Increasing chain length decreases fluidity • Increasing unsaturation increases fluidity • Cholesterol decreases fluidity

10. Figure 12-16 Snapshot of a molecular dynamics simulation of a lipid bilayer consisting of dipalmitoyl phosphatidylcholine surrounded by water. Page 393

11. Figure 12-14 Phospholipid diffusion in a lipid bilayer. Page 392

12. Figure 12-35 Asymmetric distribution of phospholipids in the human erythrocyte membrane. Page 406

13. Summary • Bilayer fluid but some lateral heterogenity probable • Bilayer provides permeability barrier to water soluble ions and molecules • Bilayer provides membrane flexibility for membrane fusion/fission • Bilayer lipids are asymetrically distributed • Big question: why so many different lipids (~400 in red blood cell)--some lipids are involved in signaling

14. Liposomes & therapy

15. Figure 12-13a Lipid bilayers. (a) An electron micrograph of a multilamellar phospholipid vesicle in which each layer is a lipid bilayer. Page 391

16. Figure 12-13b: Lipid bilayers. (b) An electron micrograph of a liposome. Page 391

17. Membrane proteins

18. General functions • Transport • Enzymatic • Structural [e.g. adhesion proteins embedded in the membrane] • Signal transduction via membrane receptors (note:multiple functions often coupled in the same protein)

19. Amount of protein varies

20. Classification of membrane proteins (peripheral vs. integral)

22. Figure 12-36 SDS–PAGE electrophoretogram of human erythrocyte membrane proteins Page 407 Coomassie blue staining (protein) PAS (periodic acid-Schiff’s reageant) (carbohydrate)

23. How are proteins associated with membranes? • Membrane spanning sequences • Electrostatic interactions (peripheral) • Lipid linkages

24. Figure 12-21 The amino acid sequence and membrane location of human erythrocyte glycophorin A. Page 397

25. Figure 19-14 General structure of a G protein-coupled receptor (GPCR). Page 674

26. Figure 12-25a Structure of bacteriorhodopsin. (a) The electron crystallography–based structure. Membrane-spanning regions are usually alpha helices Page 399

27. Figure 12-27a X-Ray crystal structure of the E. coli OmpF porin. (a) A ribbon diagram of the monomer. Another spanning motif is the beta barrel Page 401

28. Proteins are often multi-subunit

30. General types of lipid linkages

31. Types of hydrocarbon linkages

33. Figure 12-30 Core structure of the GPI anchors of proteins. Page 404

34. Thy-1 Structure Rudd et al. (1999) Glycobiology 9: 443 thanks to Pauline Rudd & Mark Wormald

36. Mobility of membrane proteins Page 396 Proteins can rotate about axes perpendicular to plane of membrane but they don’t flip- flop. They can move laterally by diffusion except when….

37. Figure 12-37d The human erythrocyte cytoskeleton.(d) Model of the erythrocyte cytoskeleton. Page 409 …they are anchored to the cytoskeleton

38. Membrane fusion important… • In targeting synthesized proteins to their sites of action • In pathology (viral infection, e.g. HIV) • Technically--producing hybridoma cells to make monoclonal antibodies

39. MEMBRANE FUSION Docking, close approach Merged compartments, membranes Destabilization fusogens Ca2+ PH ↓ Proteins (fusion machines) proteins ions

40. Figure 12-20 Schematic diagram of a plasma membrane Page 396 dates back to Singer-Nicholson Fluid Mosaic model