BIOL 408 Ch. 10 Fluid Mosaic Model of Biomembranes PDF

Ch. 10 -​ Fluid mosaic model of biomembranes -​ Covalent binding of proteins to lipids may happen via GPI anchor or via palmitoylation, myristoylation, or prenylation -​ Plasma membrane: -​ ~ 3 nm thick -​ Hydrophobic core of the bilayer prevents unassis...

Ch. 10 -​ Fluid mosaic model of biomembranes -​ Covalent binding of proteins to lipids may happen via GPI anchor or via palmitoylation, myristoylation, or prenylation -​ Plasma membrane: -​ ~ 3 nm thick -​ Hydrophobic core of the bilayer prevents unassisted movement of most water-soluble substances. -​ Hydrophilic heads connected by non-covalent interactions -​ Lipid anchored proteins are connected to one leaflet by covalently attached hydrocarbon chains -​ Peripheral proteins associate with membrane through non-covalent interactions -​ NEVER have a free edge -​ Helps to maintain separate electric charge across the plasma membrane -​ Study of phospholipid bilayers -​ Micelle treated with organic solvent (chloroform:methanol) separates proteins and oligosaccharides from phospholipids. This can be placed into water to form planar layer or liposome -​ Faces of cellular membrane -​ Only three organelles are enclosed by two membranes: -​ Nucleus, mitochondria, and chloroplasts. -​ Membrane lipids: -​ Phospholipids​ -​ Glycerophospholipid: Glycerol backbone, 2 fatty acid tails, a phosphate and -OR -​ Three most common head groups: Phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine -​ * some glycerophospholipids have ether-linked fatty acids  -​ The plasmalogen are a group of phosphoglycerides that contain one fatty acyl chain attached at C-2 of glycerol by an ESTER linkage and one long hydrocarbon chain attached to C-1 of glycerol by an ETHER (found in nervous, immune, and cardiovascular system) -​ Sphingophospholipid: Sphingosine backbone, 1 fatty acid, phosphate attached to choline -​ Glycolipid -​ Sphingoglycolipid: sphingosine backbone, 1 FA, mono-/oligosaccharide -​ Sterols -​ Four-ring sterol backbone, 1 FA, polar head group -​ Sphingolipids -​ Ceramide -​ Cerebroside -​ Gangliosides are responsible for determining human blood groups (O, A, and B). Ganglioside = Ceramide + multiple sugar-head groups. -​ O: Fucose -​ A: N-acetyl galactosamine -​ B: Galactose -​ Cholesterol -​ OH group makes it AMPHIPATHIC -​ Contribute to membrane fluidity based on temperature -​ Lipid Composition -​ E. coli plasma membrane has no Phosphatidylcholine, Sphingomyelin, or Cholesterol. ONLY Phosphatidylethanolamine and Phosphatidylserine -​ Human and animal plasma membranes contain all -​ Pure sphingomyelin(SM) layer is thicker than one formed by phosphoglyceride such as phosphatidylcholine(PC) -​ Cholesterol does not affect thickness of sphingomyelin -​ PC in exoplasmic leaflet and PE in cytoplasmic leaflet make membrane curvy -​ Phospholipase -​ A1 and A2 cleave ester bond at C1 and C2, respectively -​ Phospholipase C and D cleave one of the phosphodiester bond in head group -​ Prostaglandins​ -​ Belong to group called eicosanoids -​ Derived from fatty acid arachidonic acid (omega-6 FA) -​ Lipid Droplets -​ Lipid droplet formation begins with accumulation of cholesterol esters and triglycerides within the hydrophobic core of the lipid bilayer. -​ Transmembrane proteins -​ Most transmembrane proteins have α-helices with hydrophobic side chains interacting with the bilayer's fatty acyl chains via van der Waals forces. The hydrophilic peptide bonds are inside the helix, forming hydrogen bonds between carbonyl and amide groups. Polar groups are shielded from the membrane’s hydrophobic interior. -​ Annular Phospholipids -​ Annular phospholipids form a lipid layer directly surrounding integral membrane proteins. -​ Ex. Aquaporin O surrounded by dimyristoylphosphatidylcholine (DMPC) -​ Charged residues -​ Charged residues can guide assembly of higher order structures -​ Ex. T cell Receptors -​ Porins -​ Multiple !strands in porins form membrane-spanning ‘barrels’. -​ Found in outer membrane of Gram-negative bacteria, mitochondria and chloroplasts. -​ All porins form homotrimers in the outer membrane -​ Detergents -​ Protein Removal – Membrane proteins can be extracted using detergents or high-salt solutions. -​ Purification Challenge – Membrane proteins are difficult to isolate due to their tight association with lipids and other proteins. -​ Detergent Action – Amphipathic detergents intercalate into the bilayer, solubilizing lipids and proteins. -​ Hydrophobic & Hydrophilic Interactions – The hydrophobic part interacts with hydrocarbons, while the hydrophilic part interacts with water. -​ Types of Detergents – ​ Ionic detergents (e.g., SDS) disrupt ionic & hydrogen bonds. ​ Nonionic detergents (e.g., Triton X-100, octylglucoside) lack a charged group. -​ Micelle Formation – At low concentrations, detergents exist as single molecules; above the Critical Micelle Concentration (CMC), they form micelles. -​ Four most common detergents -​ Ionic -​ Sodium deoxycholate -​ SDS -​ Nonionic -​ Triton X-100 -​ Octylglucoside -​ Phospholipid synthesis in the ER membrane -​ Fatty Acid Activation ○​ Acyl transferase I converts fatty acid + CoA into fatty acyl-CoA. -​ Formation of Phosphatidic Acid ○​ Acyl transferase II adds fatty acyl-CoA to glycerol-3-phosphate, forming phosphatidic acid. -​ Conversion to Diacylglycerol (DAG) ○​ Phosphatase removes a phosphate group from phosphatidic acid, producing diacylglycerol. -​ Formation of Phosphatidylcholine ○​ Choline phosphotransferase transfers phosphocholine from CDP-choline to DAG, forming phosphatidylcholine. -​ Proposed mechanisms of transport of cholesterol and phospholipids between membranes -​ Vesicle transfers lipids between membranes -​ Lipid transfer is the consequence of direct contact between membranes that is mediated by membrane-embedded proteins -​ Transfer is mediated by small lipid transfer proteins