Biomembrane Structure 2024

Biomembrane Structure  discussion Components of bio membranes Function - tonicity structure Lipid composition – cell membrane heterogeneity Proteins – protein asymmetry  Review of Cell Membranes Membranes are an integral component of all cells Prokaryotic cell m...

Biomembrane Structure  discussion Components of bio membranes Function - tonicity structure Lipid composition – cell membrane heterogeneity Proteins – protein asymmetry  Review of Cell Membranes Membranes are an integral component of all cells Prokaryotic cell membranes: – Prokaryotic cells are surrounded by a single plasma membrane, in most cases, they contain no internal membrane sub-compartments Review of Cell Membranes Prokaryotic cell membranes: Contains 100s of proteins integral to cell function catalyze ATP synthesis initiation of DNA replication membrane transport proteins - allow specific ions, sugars, amino acids and vitamins to cross Receptor proteins - these allow the cell to recognize chemical signals present in it’s environment  Review of Cell Membranes Eukaryotic cell membranes: – plasma membrane surrounding cell are studded with proteins with various functions membrane transport proteins receptors for chemical signaling adhesion molecules (to extracellular components & cytoskeleton) bio membranes are also found within cytoplasm surrounding organelles Eukaryotic Cellular Membranes Functions of the Membrane (Eukaryotes) Contribute to shape of the cell and organelles Stability – hydrophobic & van der Waals interactions between lipid chains provides strength that allows membrane to retain its architecture Selectively-permeable barrier Concept of tonicity – Isotonic – Hypertonic – Hypotonic Biomembrane Variation in Different Cells Smooth PM on RBC Ciliated projections on brain ventricle ependymal cells  Biomembrane Structure All biomembranes share common structural features – Phospholipids spontaneously form bilayers – Lipid bilayer embedded with many types of proteins – Each lipid layer is called a leaflet a bilayer = 2 leaflets  Lipids & Proteins are Laterally Mobile Fluorescence recovery after photobleaching (FRAP) experiments quantify movement of lipids & proteins with plasma membrane Bilayer Structure of Biomembranes Other Phospholipid Structures in H2O Cross-sectional view of two structures formed by dispersal of phospholipids in water. Micelle has a hydrophobic interior composed entirely of fatty acyl chains A spherical liposome consist of phospholipid bilayer surrounding an aqueous center Faces of Cellular Membranes Faces of Cellular Membranes are Conserved  Membrane Lipid Composition 3 general classes of membrane lipids: Phosphoglycerides Sphingolipids Sterols (Cholesterol) Membrane lipids are amphipathic  Phosphoglycerides Phospholipids are amphipathic: consist of 2 segments with very different chemical properties: – Hydrophobic hydrocarbon tails of fatty acid side chains keep away from H2O – Hydrophilic head groups interact w/ H2O Phosphoglycerides have various head group attachments to phosphate group: – Choline is the most common attachment  Fatty Acids of Phospholipids Fatty acids: long chains of hydrocarbons w/ carboxyl group at 1 end – Length of fatty acids: 14, 16, 18 or 20 carbons – Degree of saturation: 0, 1, 2 or 3 double bonds Plasmalogens have 1 fatty acid attached by an ether linkage and one by an ester linkage. – Synthesized on the peroxisomal membrane – Fatty acid components of plasmalogens are structural precursors for signaling molecules Figure 7-8a: Phosphoglycerides phosphatidylethanolamine phosphatidylcholine phosphatidylserine phosphatidylinositol  Sphingolipids Derived from sphingosine: an amino alcohol w/ long hydrocarbon chain – sphingosine made in the ER Sphingomyelin (most common) has a phosphocholine head group Glycolipids (glycosphingolipid) polar head groups are sugars – Gangliosides are complex glycolipids w/ branched sugars Sphingolipids SM = sphingomyelins GlcCer = glucosylcerebroside  Sterols Cholesterol: most abundant single lipid in mammalian PM – forms the basis for a wide variety of molecules, including fat- soluble vitamins, bile acids and steroid hormones 4 ring hydrocarbon amphipathic molecule – Conjugated ring w/ short hydrocarbon chain: hydrophobic tail – OH group like a polar head group – Interdigitates between phospholipids in inner and outer leaflets Lipid Composition Influences Physical Properties of Membranes Membrane fluidity decreases w/ sphingolipids and cholesterol – Cholesterol helps maintain structural integrity of plasma membrane, including at temperature extremes Membrane fluidity increases with phosphoglycerides Lipid composition of a membrane also influences thickness and curvature See Figure 7-11  Lipid Distribution Membrane lipid distribution is asymmetrical between exoplasmic and cytoplasmic leaflets – Reasons for uneven distribution are unknown – Cholesterol is fairly evenly distributed Flippases are involved in asymmetrical distribution of membrane phospholipids. – Move phospholipids from one leaflet to the other in membranes – ATP-powered transport proteins ABC superfamily class of pumps – Changes to phospholipid distribution involved in apoptosis and cellular destruction by scavenger cells.  Asymmetry of Membrane Lipids Phospholipids Glycolipids – PC, Sphingomyelin mainly in – Exclusively in outer leaflet outer leaflet Cholesterol – PE, PI mainly in inner leaflet – PS exclusively in inner – Evenly distributed on inner leaflet and outer leaflets  Lipid Rafts Regions of cell membrane where specific lipids & proteins enriched – Lipids = cholesterol, sphingolipids (sphingomyelin, glycolipids) signal transduction: facilitate signaling by certain PM receptors decreased membrane cholesterol content may lead to dissolved rafts  Membrane Proteins Kinds and amounts of proteins in membranes vary depending on cell type and subcellular localization Interacts w/ membranes in 3 ways: 1. Peripheral 2. Integral 3. Lipid-anchored Plasma membrane = 50% Mitochondria = 75%  Transmembrane Proteins Transmembrane proteins are integral proteins that span membrane with 3 distinct regions: – 2 hydrophilic exterior regions to interact w/ H2O – 1 hydrophobic interior to span membrane; hydrophobic aa side chains interact w/ membrane fatty acid tails Hydrophobic α-helix most common secondary structure of transmembrane proteins – Hydrophobic interactions, Van der Waals Single-Pass Vs. Multi-Pass proteins Single-pass vs. Multi-pass Proteins Transmembrane proteins and glycolipids are asymmetrically distributed in the bilayer – Glycoproteins and glycolipids are only found in the exoplasmic face of the plasma membrane. Typical Single-pass Transmembrane Protein Glycophorin A: Protein in rbc PM Heavy glycosylation on Serine Threonine, asparagine residues 23aa membrane spanning - helix w/ hydrophobic uncharged aa Arginine & Lysine residues help anchor in membrane Dimer!  Multipass Membrane Protein Protein goes through the membrane multiple times – Bacteriorhodopsin has 7 hydrophobic helices  Porins Another class of transmembrane protein Do not contain hydrophobic α-helices They have – hydrophilic interior – hydrophobic exterior Most porins are Trimeric – 3 identical subunits of -strands that form sheets that twist into barrel- shaped structure w/ central pore Examples: – Mitochondrial porin Structural model of 1 subunit – OmpX: porin found in E.coli OM of OmpX  Aquaporins Aquaporins are different – Tetramers – Multiple transmembrane -helices – Transport water, glycerol and other hydrophilic molecules Anchored Membrane Proteins by Covalently Linked Hydrocarbons (c) Exoplasmic face to GPI (glycolipids) – Glycosylphosphatidylinositol (a) Fatty acyl group attach to N term glycine. Anchors:(Myristate(C14) and palmitate (C16) are common acyl anchors (b) Hydrocarbon chain attach to cysteine residue at C terminus. Anchors: farnesyl(C15) and geranylgeranyl(C20)  Human ABO Blood Group Antigens Oligosaccharide chains covalently attached to glycolipids or glycoproteins in PM Terminal oligosaccharide sugars distinguish 3 antigens Presence or absence of glycosyltransferases that add galactose or GalNAc to O Antigen determines blood type Different blood types in US & Canadian populations Canada United States of America total Caucasian African American Hispanic Asian O+ 39% 37% 47% 53% 39% O- 7% 8% 4% 4% 1% A+ 36% 33% 24% 29% 27% A- 6% 7% 2% 2% 0.50% B+ 7.60% 9% 18% 9% 25% B- 1.40% 2% 1% 1% 0.40% AB+ 2.50% 3% 4% 2% 7% AB- 0.50% 1% 0.30% 0.20% 0.10% Information taken from the Canadian Blood Services and American Red Cross  Detergents Detergents are amphipathic molecules that disrupt membranes by intercalating into phospholipid bilayers and solubilize lipids and many membrane proteins proteins can be removed from membranes with detergents – Ionic detergents denature proteins – Non-ionic solubilize integral membrane proteins Yellow: Hydrophobic part attracted to hydrocarbons Blue: Hydrophilic part strongly attracted to H2O Sodium deoxycholate – bile salt is a natural product Principles of Membrane Biosynthesis New bio membranes are synthesized by expanding pre-existing membranes Many lipids are synthesized on the membranes of the smooth ER Final steps of membrane lipid synthesis takes place on destination membranes After synthesis, membrane lipids must be distributed to the appropriate leaflet & organellar membranes  Fatty Acid Synthesis Fatty acids can be synthesized from: – the enzymatic hydrolysis of triacylglycerol which is stored in adipocytes in mammals and other vertebrates, – or de novo from Acetyl CoA 14 and 16C fatty acids are synthesized in the cytosol by Acetyl-CoA carboxylase and fatty acid synthase. – Palmitoyl CoA (16C) can be elongated to 18-24C in the smooth ER membrane. All newly synthesized fatty acids are saturated. – Addition of double bonds occurs in the ER membrane by desaturase enzymes.  Intracellular Movement of Fatty Acids Fatty acids move within cells bound to cytosolic proteins called fatty acid binding proteins (FABPs). – Bind to hydrophobic pocket with which a long fatty acid chain can interact FABPs are up-regulated and down- regulated depending on the cellular requirements for the uptake and release of free fatty acids. A cell using fatty acids for respiration, FABP: ribbon diagram or an adipocyte releasing fatty acids, Fatty acid: yellow contains large numbers of FABPs 2 Oxygens: red within the cytosol.  Synthesis of Phospholipids Fatty acids converted into fatty acyl CoAs (CoA esters). 1. Fatty acyl CoA + glycerol phosphate are converted to phosphatidic acid by acyl transferases (esterases) on the smooth ER membrane. 2. Membrane phosphatase: converts phosphatidic acid to diacylglycerol 3. Choline phosphotransferase: transfers phosphocholine to diacylglycerol to form the phospholipid. 4. Flippase: transfers lipids from cytosolic leaflet to exoplasmic leaflet Cholesterol Synthesis Cytosolic acetyl CoA combines with acetoacetyl CoA forming HMG-CoA HMG-CoA converted to 6C mevalonate by HMG-CoA reductase HMG-CoA reductase embedded in SER membrane but has catalytic domain in cytosol Cytosolic enzymes convert mevalonate to IPP, Farnesyl pyrophosphate and squalene Squalene converted to cholesterol on SER membrane  Atherosclerosis Hardening of the arteries caused by blockage of arterial lumen Major cause of heart disease in the industrialized West Steps: – damage to endothelial cells – monocyte entry & conversion to macrophages – uptake of LDL – conversion to foam cells – foam cells accumulate – plaque formation Anti-atherosclerosis medications include statins – Bind to HMG-CoA reductase and directly inhibit its activity, so there is reduced cholesterol biosynthesis Transport of Lipids b/w Organelles Some cholesterol & phospholipids are transported via Golgi- dependent processes, especially if lipids bound to proteins 3 Golgi-independent mechanisms have been proposed for most lipid transport b/w organelles: (Figure 7-27) – via vesicles – direct contact b/w membranes mediated by integral proteins – mediated by soluble lipid-transfer proteins  q1 Which statements accurately describe membrane proteins? Select all that apply. A. All peripheral membrane proteins are predominantly hydrophobic. B. All integral membrane proteins are amphipathic. C. All transmembrane proteins are also integral membrane proteins. D. All transmembrane proteins contain a hydrophilic core that allows specific ions to pass through.  Q2 Which of the following components of biological membrane are amphipathic? Please select all that apply. a) Integral membrane proteins b) Phospholipids c) Glycolipids d) Membrane steroids such as cholesterol, sitosterol and ergosterol  Q3 Which of the following applies to membrane lipids? Please select all that apply. a) Membrane lipids are composed of hydrophobic molecules. b) Flippases are able to catalyze the transfer of lipid molecules between the outer and inner leaflets. c) Membrane lipids are able to spontaneously move between the outer and inner leaflets. d) Different lipid compositions are found in the two leaflets of a membrane.  Q4 In the plasma membrane, Glycolipids are usually situated in (a) cannot be predicted, it varies according to the cell types (b) inner leaflet of the plasma membrane (c) the outer leaflet of the plasma membrane (d) evenly distributed in both outer and inner leaves of plasma membrane