BMB 462 1st Edition Lecture 4 Outline of Last Lecture I. Experimentation with LipidsII. Membrane FunctionIII. Membrane Structure & Compositiona. Common featuresb. Lipid Compositionc. Fluid Mosaic Modeld. Protein CompositionIV. Introduction to Hydropathy PlotsOutline of Current Lecture I. Review of Hydropathy PlotsII. Fluid Mosaic Modela. Additional proteinsb. Membrane dynamicsIII. Membrane FusionCurrent LectureConcepts to remembers from previous courses/lectures:I. Review of Hydropathy Plotsa. Both the inside and the outside of a membrane are polar, the inner portion of the membrane is hydrophobici. To cross the membrane, a protein must be partially hydrophobic (to fit in the inner membrane) and partially hydrophilic (to interact with the aquatic exteriorsii. If there are 5 peaks in a hydropathy plot, you like have a protein with 5 alpha-helices1. the protein crosses the membrane 5 times, so the N-terminus and the C-terminus will be on opposite sides of the membraneiii. Beta-barrel proteins are approximately 20+ transmembrane segments that line a columnThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.1. It only takes about 7-9 amino acids to make it across the entire membrane2. Alternating amino acids are hydrophobic/hydrophilic, alternately facing the bilayer and lining the cylinder.a. Because of this, hydropathy plots do not show beta-barrelsiv. Polar residues include serine, glutamate, and lysine. Nonpolar residues include phenylalanine and leucine.II. Fluid Mosaic Modela. Additional proteinsi. Amphitrophic Proteins: these are sometimes peripheral, sometimes found in the cytosol1. Signaling determines where these proteins are ultimately foundii. Lipid-Linked proteins1. These proteins are bonded to a lipid in the membrane2. They function while connected to the membrane, act like integral proteinsa. Typically, to be removed, the membrane has to be disrupted (this is not always so, though, i.e. when linked to 1 fatty acid, there isn’t much force needed to separate the protein)3. Lipid-linked proteins contain fatty acid linkages, isoprenoid linkages (bio-ether bonds), GPI linkages (glycosylated phosphatidylinositol)a. GPI linkages are always outside, other bonds are always found inside the membrane. Some GPIs are linked to organelle membranesi. These do not flip flop in the membrane!b. Membrane dynamicsi. Gel vs Liquid state1. Gel state is highly ordered, there is little motion. a. The acyl chain movement is staticb. The membrane loses flexibility and runs the risk of breaking apart2. A fluid state is characterized by a lot of motiona. The components are packed tightb. A very fluid membrane can let molecules in the cell doesn’twant, and can fall apart3. Membrane thickness changes with temperature changesa. Temperature and fluidity is a direct relationship; as temperature increases, membrane fluidity increases, and vice versa4. Lipid composition also impacts fluiditya. As unsaturation increases, fluidity increasesb. As the number of short carbon chains increases (and the number of long carbon chains decreases), fluidity increasesc. Things that decrease melting point increase fluidityii. Regulation of Membrane fluidity1. As temperature increases, E. coli can regulate/change the amount of saturated vs. unsaturated lipids to decrease (or increase, as temperatures decrease) fluidity2. At colder temperatures, cells need more fatty acids that increase membrane fluiditya. i.e. palmitate is a shorter fatty acid, linoleate has more double bonds than oleate, etciii. Transverse diffusion energetics1. For a lipid to move transversely, the polar head has to go through the hydrophobic corea. This makes the movement thermodynamically unfavourable and slow! (it takes ½ a day to move to the opposite leaflet and requires help from enzymes)2. Transverse diffusion of proteins does not happena. Anchored proteins do not diffuse much; if they are not anchored they will move laterally but much slower than lipidsb. Cytoskeletal proteins against the membrane cause an energetic barrier to protein movementiv. Lateral diffusion energetics1. In a liquid crystal state, there is a lot of lateral movementa. Because there are no covalent bonds to hold them steady, it doesn’t require energy to move, so 1 phospholipid can move around a whole E. coli in ~1 second2. Protein corrals restrict lateral movement3. Sphingolipid and cholesterol microdomains (rafts) a. These types of lipids like to cluster into ‘rafts’ and the clustering hinders lateral movementb. Cholesterol is a rigid structure but has broad rings, so it likes to pack in tightly with saturated fatty acids.4. Caveolina. These are integral membrane proteinsb. Function: the create invaginations/cavities in the membrane called caveolaei. Used for endocytosis and signal transductionIII. Membrane Fusiona. This is the process of 2 originally distinct and separate lipid bilayers merging together their hydrophobic cores.b. It is useful for endocytosis, phagocytosis, transporting nutrients and waste via vesicles, fertilization (joining of the egg and sperm)c. Role of Membrane proteinsi. SNAREs are main proteins involved in fusion, though the exact role is not well known1. Stands for SNAP (Soluble NSF Attachment Protein) Receptor2. They mediate membrane fusion with vesicles. ii. Proteins are also key in signal transduction and cell-cell
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