CBS Lipids and membrane structure KEATS 23_24 PDF

Add Portrait Photo Faculty of Life Science and Medicine Stuart Knight Foundations of Medical Science Cell Biology and Signalling block Biochemistry Department Lipids and...

Add Portrait Photo Faculty of Life Science and Medicine Stuart Knight Foundations of Medical Science Cell Biology and Signalling block Biochemistry Department Lipids and Membrane Structure Dr Stuart Knight Learning Outcomes Recognise the main classes of lipid structures (saturated and unsaturated fatty acids, triacylglycerols, phospholipids, glycolipids and cholesterol) Outline the 'fluid mosaic model' of membrane structure Describe the main biochemical components of membranes and their orientation Indicate the major characteristics of membrane proteins (integral, anchored and peripheral) Describe how different methods can be used to analyse membrane proteins Appreciate the importance of abnormal metabolism of membrane components in disease Dr Stuart Knight 2 Membranes of a cell  Composition of membranes Phospholipids major components of all membranes Spontaneous form bi-layer in aqueous environment Composed of a “polar head group” that is attached to a backbone (glycerol) through a phosphate group Two fatty acyl side chains are linked to the glycerol backbone via ester bonds They are “Amphipathic” : polar head group and non-polar FA tail Fluid mosaic model of membrane structure “Islands of protein in a sea of lipid”  Fluid mosaic model of membrane structure “Islands of protein in a sea of lipid” CARBOHYDRATE PHOSPHOLIPID 4-5nm PROTEIN  Variation in composition of cellular membranes Plasma Outer mitochondrial Inner mitochondrial Nuclear membrane membrane membrane membrane Carbohydrate 8 0 0 0 (% of membrane) Protein : Lipid ratio 1 1 3 3 Lipids (%) PC 18 45 50 55 PE 9 2 1 3 SPH 14 5 2.5 3 Cholesterol 30 5 2.5 10 Others 29 43 43.5 29  Lipid bilayers are asymmetrical Glycolipid two halves of the bilayer have different lipid composition PC and SPH face the extracellular environment PS and PE face the cytosolic side  Membrane fluidity Fluidity is the ease with which lipid molecules move about in the plane of the bilayer – important in the regulation of membrane function (e.g. movement of proteins, signalling, exocytosis)  Regulation of fluidity Lipid composition of membrane defines its fluidity Increase in short chain fatty acids reduce the van der Waals interactions between fatty acids and increases fluidity Kinks in unsaturated fatty acids reduce van der Waals interactions with other lipids and increases fluidity High cholesterol content restricts the random movement of polar heads, orders the lipid bilayer and decreases fluidity – rich in highly ordered regions of the membrane lipid rafts  Lipid Rafts Specialised membrane microdomain More ordered – less fluid Increased level of cholesterol Increased level of sphingomyelin and gangliosides Allows close interaction between receptors and signalling molecules outside cell inside cell Lipid raft https://en.wikipedia.org/wiki/Lipid_raft  Types of membrane protein Type Function Examples Cell-cell contact; Structural attachment of actin, spectrin, ankyrin cytoskeleton Signal recognition and Insulin receptor, Glucagon Receptors transmission receptor Maintenance of ionic Acetylcholine (nicotinic) Ion channels gradients and receptor, GABAA receptor transmission Import and export of Transporters glucose transporters substrates Enzymes catalysis adenylate cyclase  Organisation of membrane proteins Integral (intrinsic) proteins – embedded in lipid bilayer, most span the entire bilayer. Transmembrane spanning domains are α-helices or β-sheets (1-4) Anchored proteins – anchored to membrane by covalent bonds with fatty acids (5-6) Peripheral (extrinsic) proteins – attach to membrane surface by ionic interactions with integral proteins or with polar head group of phospholipids (7-8)  Integral membrane protein Non-polar side Polar side chain chain  Anchored proteins Not deeply embedded in the bilayer but covalently linked to fatty acid chains or on the cell surface to glycolipid – Example of a glycolipid anchored protein: the enzyme alkaline phosphatase – Example of a fatty acyl anchored protein: RAS a signalling G-protein  Peripheral proteins Peripheral membrane proteins attach to the membrane surface by interactions with other membrane proteins or with the polar head group of phospholipids – spectrin: important structural protein on the cytoplasmic surface of erythrocytes interacts with other proteins such as ankyrin How different types of proteins can be removed from membranes Treatment Peripheral Anchored Integral High Salt, Urea, Removed Remain Remain Detergent Removed Removed Removed Phospholipases Removed or Removed Remain Remain Removal of proteins from lipid bilayer by detergents  Phospholipases Important class of enzymes that bind to membrane and selectively hydrolyses components of phospholipids – Phospholipase A1 (PLA1) – Phospholipase A2 (PLA2) – Phospholipase C (PLC) – Phospholipase D (PLD)  X PLD Site of action of P phospholipases O PLC sn-1 sn-2 O O PLA1 PLA2 O O (X=choline, ethanolamine, myo-inositol) PLA : phospholipase  Case based discussion The details of the case will be presented in class and released on KEATS at the end of the lecture  Summary Fluid mosaic model Composition of membrane Fluidity of membranes Proteins and membranes Analysis of membrane proteins