BIOC 460, Spring 2008LEC 19, Membranes 2 - MembraneProteins 1Lecture 19Membranes 2:Membrane ProteinsNext 2 lectures: Membrane TransportReading: Berg, Tymoczko & Stryer, 6th ed., Chapter 12, pp. 336-348Bacteriorhodopsin Jmol structure:http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/rhodopsin/rhodop1.htmPGH2 Synthase (COX 2) Jmol structure:http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/cox12/cox121.htmBacterial porin Jmol structure:http://www.biochem.arizona.edu/classes/bioc462/462a/jmol/porin/newporin.htmlKey Concepts• Membrane functions (review): selective permeability barriers,information processing, organization of reaction sequences, energyconversion• Lipids (lipid bilayer) responsible for permeability barrier• Proteins perform essentially all other membrane functions, includingmodulation of permeability barrier by allowing or assisting some solutes tocross membrane (transport processes)• Fluid mosaic model of membrane structure: 2-dimensional "fluid"composed of lipids and proteins (both often with attached carbohydrateson outer side of membrane)• Proteins: peripheral, lipid-anchored, or integral• Mobility of components within the membrane:– Lateral diffusion: rapid for both proteins and lipids within the planeof the membrane (except for proteins anchored, for example tocytoskeleton)– Transverse diffusion ("flip-flop") of both proteins and lipids isextremely slow, unless mediated by protein "flippases".– Lipid composition in the 2 leaflets of bilayer is asymmetric, as isprotein distribution.Key Concepts, continued• Membrane fluidity essential to function, regulated by fatty acidcomposition of lipids and (eukaryotes) by cholesterol content• Integral membrane proteins typically assume one of two secondarystructures to get polar groups of polypeptide backbone acrosshydrophobic core of lipid bilayer: membrane-spanning α helices (about 20residues long) or antiparallel β sheets wrapped into β barrels.• Examples:– Glycophorin: single hydrophobic transmembrane α helix– Bacteriorhodopsin: 7 transmembrane helices– Prostaglandin H2 Synthase: on surface of ER membrane butanchored in membrane by a set of α-helices with hydrophobic Rgroups that extend into membrane core– Porins: large β barrel with aqueous channel down the centerLearning Objectives• Terminology (as applied to membrane proteins): peripheral, integral,lipid-anchored (operational definition -- how can they be extractedfrom membrane?); trans-membrane helix; antiparallel β barrel• Briefly explain what “lipid rafts” are in membranes.• Explain in structural terms how an integral membrane protein can dealwith its polar backbone groups in spanning the hydrophobic core of alipid bilayer.• Name 2 types of secondary structural elements used by integralmembrane proteins to cross membranes. Describe where the Rgroups are located in these secondary structural elements relative tothe hydrophobic lipid core.• Discuss the structural properties of the following examples ofmembrane proteins: glycophorin A, bacteriorhodopsin, prostaglandinH2 synthase, and a porin. Include in your discussion the type(s) ofsecondary structure and types of R groups found in thetransmembrane (membrane-spanning) structural components of thesemembrane proteins.Lipid Rafts• lateral diffusion (sideways in plane of membrane) rapid for lipids and formany proteins (but NOT for proteins "anchored" by attachment to otherproteins, e.g., in cytoskeleton on inner side of membrane, or extracellularmatrix, or both -- e.g., fibronectin)• Timescale of msec to sec, lipids DO diffuse freely in plane of membrane.• On much shorter time scale, 25 µsec intervals, lipids zoom around in a smallconfined area of membrane, then seem to "hop" to another small confinedarea, as if there were "fences" they had to hop over (networks of interactingmembrane proteins?)• Very recent research: different types of membrane lipids are NOT randomlylocated all through the membrane -- some phosphosphingolipids andcholesterol cluster together in membrane ”rafts" (patches of lipid about 50nm wide), thicker and more "ordered" structurally than the more disorderedneighboring microdomains rich in glycerophospholipids.• Lipid rafts have a few thousand lipid molecules and about 10-50 proteinmolecules, and are particularly enriched in 2 classes of lipid-anchoredintegral membrane proteins.• Rafts may "organize" some membrane receptors and signaling proteinswhose functions require protein-protein interactions (collision probabilitymuch greater in "corral" of local raft).• Proteins and lipids move in and out of rafts, but on slower time scale (secrather than µsec), but biochemical processes work on the faster time scalein which rafts are stable clusters.Membrane Proteins• mediate nearly all membrane functions except establishment ofpermeability barrier• membrane protein functions:– "pumps" (active transport)– "gates" ("passive" transport, facilitated diffusion)– receptors– signal transduction– enzymes– energy transduction• Membrane protein distribution:– Both amount of protein in general and which specific proteins arepresent varies with function of membrane, i.e., with type ofmembrane and with cell type.– Examples:• myelin (membrane around myelinated nerve fibers,function=electrical insulation) mostly lipid (only ~18% protein)• plasma membrane: enzymes, receptors, etc. (~50% protein)• mitochondrial inner membrane and chloroplast thylakoidmembrane: electron transport, energy transduction (ATPsynthesis) (~75% protein)BIOC 460, Spring 2008LEC 19, Membranes 2 - MembraneProteins 2Nelson & Cox, Lehninger Principles of Biochemistry, 4th ed., Fig. 11-3Schematic Diagram of Membrane StructureFluid Mosaic Model of Membrane Structure(Singer and Nicholson, 1972)• Carbohydrates on both proteins (glycoproteins) and lipids (glycolipids) are exposed on extracellular surface of plasma membrane.but transverse diffusion ("flip-flop") is very slow unless there's a catalyst for it.• model of biological membranes as 2-dimensional "solutions" ofglobular proteins embedded in fluid lipid bilayer, structurally andfunctionally asymmetric with respect to the 2 sides of bilayer• Fatty acyl chains in interior of membrane form a fluid, hydrophobicregion; surface is hydrophilic.• Proteins and lipids can diffuse laterally (in plane of membrane) unlessthey're "anchored" to something,Nelson &
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