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UCLA CHEM 153A - Biological Membranes & Transport

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Chapter 12Biological Membranes & TransportFor chapter 12Focus on the material covered in lecturesWill not be tested on materials covered in Pages 424 - 429Fluid Mosaic Model for Membrane StructureAmphipathic lipid aggregates that form in water or VesicleBilayers are noncovalent, cooperative structuresMonolayer of oil molecules at an air-water interfaceThe "melting" of membrane lipids• Below a certain transition temperature, membrane lipids are rigid and tightly packed • Above the transition temperature, lipids are more flexible and mobile • The transition temperature is characteristic of the lipids in the membrane Membrane Phase TransitionsHigher the proportion of saturated fatty acid, higher is the transition temperature.Sterol content of a membrane has 2 effects on membrane fluidityBelow the transition temperature: Insertion of rigid planar sterol prevents highly ordered packing of fatty acid side chains Membrane fluidityAbovethe transition temperature: Rigid planar sterol reduces the freedom of neighboring fatty acid side chains Membrane fluidityCells regulate their lipid composition to achieve a constant membrane fluidity under various growth conditionsLateral DiffusionTransbilayerorflip-flop DiffusionMotion of Membrane LipidsA relatively new discovery! Lipids can be moved from one monolayer to the other by flippase proteins  Some flippases operate passively and do not require an energy source  Other flippases appear to operate actively and require the energy of hydrolysis of ATP FlippasesDemonstration of lateral diffusion of membrane proteinsMembrane proteins, like membrane lipids, are free to diffuse laterally in the plane of the bilayerRestricted motion of the erythrocyte chloride-bicarbonate exchangerAsymmetric distribution of phospholipids between the inner & outer monolayers of erythrocyte plasma membraneStructure of Membrane ProteinsSinger & Nicolson defined two classes- Integral (intrinsic) proteins - Peripheral (extrinsic) proteins - We'll note a new one –lipid-anchored proteinsPeripheral & Integral ProteinsSome membrane proteins span the lipid bilayerGlycophorin in the erythrocyteA single-transmembrane-segment proteinC One transmembrane segment with globular domains on either end C Transmembrane segment is alpha helical and consists of 19 hydrophobic amino acids C Extracellular portion contains oligosaccharides (and these constitute the ABO and MN blood group determinants)Lipid-linked membrane proteinsCovalently attached lipids anchor membrane proteins to the lipid bilayerGlycosyl phosphatidylinositol (GPI) anchorA relative new class of membrane proteins4 types have been found: Amide-linked myristoyl anchors Thioester-linked fatty acyl anchors Thioether-linked prenyl anchors Glycosyl phosphatidylinositol anchorsIntegral Membrane ProteinsHeld in the membrane by hydrophobic interactions with lipidsBacteriorhodopsin, a membrane-spanning protein3-D structure of the photosynthetic reaction center of purple bacteriumFirst integral membrane protein to have its structure determined by X-ray diffraction methodsProsthetic group(light-absorbing pigments)Residues that are part of the trans-membrane helicesHydropathy Plots1HydropathyPlotsPorin FhuA, an integral membrane protein with β-barrel structureNot all integral membrane proteins are composed of transmembrane α helicesPorin allows certain polar solutes to cross the outer membrane of bacteriaPorinsFound both in Gram-negative bacteria and in mitochondrial outer membrane¾ Porins are pore-forming proteins (30-50 kD) ¾ Most arrange in membrane as trimers¾ High homology between various porins¾ Porin from Rhodobacter capsulatus has 16-stranded beta barrel that traverses the membrane to form the poreWhy Beta Sheets?for membrane proteins?? - Genetic economy - Alpha helix requires 21-25 residues per transmembrane strand - Beta-strand requires only 9-11 residues per transmembrane strand - Thus, with beta strands , a given amount of genetic material canmake a larger number of trans-membrane segments4 examples of integral protein types that function in cell-cell interactionServe as receptors & signal transducersIntegral membrane proteins mediate cell-cell interactions & adhesionEssential part of the blood-clotting processGap JunctionsVital connections for animal cells9Provide metabolic connections 9 Provide a means of chemical transfer 9 Provide a means of communication 9 Permit large number of cells to act in synchrony(for example, synchronized contraction of heart muscle is brought about by flow of ions through gap junctions) Hexameric arrays of a single 32 kD protein  Subunits are tilted with respect to central axis  Pore in center can be opened or closed by the tilting of the subunits, as response to stress Gap JunctionsInduces closure of gap junction central channelMembrane fusion is central to many biological processesMembranes undergo fusion without losing its integrityMembrane fusion during viral entry into a host cellMovements of solutes across a permeable membraneElectrically neutral solutesElectric gradient or membrane potentialEnergy of activationEnergy changes accompanying passage of a hydrophilic solute through the lipid bilayer of a biological membraneFacilitated diffusion or passive transportAquaporins form hydrophilic transmembranechannels for the passage of waterLikely transmembrane topology of an aquaporin, AQP-1MonomerProposed structure of aquaporin channel(Formed by 4 monomers)Water flows through the channel in single file at the rate of 5 X 108molecules / secondGlucose transporter of erythrocytes mediates passive transportProposed structure of GluT1Monomer112A helical wheel diagramShows the distribution of polar& non-polar residues on the surface of a helical segmentSide-by-side association of 5 or 6 amphipathic helicesPolarModel of glucose transport into erythrocytes by GluT1T1 & T2 are 2 different conformationsT1 has glucose binding site on the outer surface of the membraneT2, with the binding site on the inner surfaceThree general classes of transport system1) Differ in # of solutes transported& 2) the direction in which each is transportedSummary of transport typesTypes of transportPassive: Transported species always moves down its electrochemical gradient and it is not accumulated above the equilibrium pointATP not requiredActive: Results in accumulation of solute above the equilibrium pointATP is requiredThree types of ion-transporting ATPaseIn animal cells, this active


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UCLA CHEM 153A - Biological Membranes & Transport

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