Biomembrane Structure and Transmembrane Transport of Ions and Small Molecules PDF

11-13-2024 Molecular Cell Biology Biomembrane Structure and Transmembrane Transport of Ions and Small Molecules 潘玟伃 Wen-Yu Pan, Ph.D. Office:10F, Education & Research Building Phone: (02) 6620-2589#11010 E-mail：[email protected] Lodish  Berk  Kaiser  Krieg...

11-13-2024 Molecular Cell Biology Biomembrane Structure and Transmembrane Transport of Ions and Small Molecules 潘玟伃 Wen-Yu Pan, Ph.D. Office:10F, Education & Research Building Phone: (02) 6620-2589#11010 E-mail：[email protected] Lodish  Berk  Kaiser  Krieger  scott  Bretscher  Ploegh  Matsudaira MOLECULAR CELL BIOLOGY SEVENTH EDITION CHAPTER 10 Biomembrane Structure Copyright © 2013 by W. H. Freeman and Company  3 Molecular Cell Biology, 7th edition, Lodish et al.  Fluid mosaic model of biomembranes 4 Molecular Cell Biology, 7th edition, Lodish et al.  Prokaryotic cells and eukaryotic cells 5 Molecular Cell Biology, 7th edition, Lodish et al.  Eukaryotic cell membranes are dynamic structures Budding from ER 6 Molecular Cell Biology, 7th edition, Lodish et al.  Membrane fluidity 7 Essential Cell Biology (© Garland Science 2010)  Biomembrane structure  The lipid bilayer: Composition and structural organization  Membrane proteins: Structure and basic functions 8  The bilayer structure of biomembranes Erythrocyte amphipathic molecules sonication van der Waals interaction Ionic and hydrogen bond 9 Molecular Cell Biology, 7th edition, Lodish et al.  Formation and study of pure phospholipid bilayers Chloroform, methanol 10 Molecular Cell Biology, 7th edition, Lodish et al.  The faces of cellular membranes 11 Molecular Cell Biology, 7th edition, Lodish et al.  Faces of cellular membranes are conserved during membrane budding and fusion 12 Molecular Cell Biology, 7th edition, Lodish et al.  Three classes of membrane lipids Polar head group (positively charged) glycerol-3-phosphate phosphatidylethanolamine phosphatidylcholine Two esterified fatty acyl chains (16-19 carbons) phosphatidylserine Most abundant lipid Most abundant membrane lipid (PC) phosphatidylinositol sphigomyelins phospholipid glucosylceramide glycolipid Precursor for bile acid, steroid hormone short hydrocarbon chain and Vit. D 13 Molecular Cell Biology, 7th edition, Lodish et al.  Lipid 14 Essential Cell Biology (© Garland Science 2010)  Major lipid components of selected biomembranes  Phospholipid are synthesized in ER.  Sphingolipids are synthesized in Golgi complex. 15 Molecular Cell Biology, 7th edition, Lodish et al.  Membrane phospholipids are motile 16 Figure 11-15 Essential Cell Biology (© Garland Science 2010)  Gel and fluid forms of the phospholipid bilayer Below 37ºC Molecular models of phospholipid monolayer 17 Molecular Cell Biology, 7th edition, Lodish et al.  Effect of lipid composition on bilayer thickness and curvature Cholesterol increase the thickness of PC bilayer cylindrical shape conical shape 18 Molecular Cell Biology, 7th edition, Lodish et al.  Biomembrane structure  The lipid bilayer: Composition and structural organization  Membrane proteins: Structure and basic functions 19  Plasma membrane proteins have a variety of functions 20 Figure 11-20 Essential Cell Biology (© Garland Science 2010)  Proteins interact with membranes in three different ways  Integral membrane proteins  Lipid-anchored membrane proteins  Peripheral membrane proteins: Interact with integral or lipid- anchored membrane proteins or with lipid head groups 21 Figure 11-21 Essential Cell Biology (© Garland Science 2010)  Structure of glycophorin A, a typical single-pass transmembrane protein glycosylation  A glycoprotein located on the red blood cell membrane  Membrane-spanning segments with hydrophobic amino acid 22 Molecular Cell Biology, 7th edition, Lodish et al. Figure 11-23 Essential Cell Biology (© Garland Science 2010)  Charged residues can orchestrate assembly of multimeric membrane proteins Disulfide-linked homodimer 23 Molecular Cell Biology, 7th edition, Lodish et al.  Multiple b strands in porins form membrane- spanning “barrels”  In the outer membrane of E. coli  Provide channels for the passage of specific types of small molecules 24 Molecular Cell Biology, 7th edition, Lodish et al.  Anchoring of plasma-membrane proteins to the bilayer by covalently linked hydrocarbon groups (Glycosylphosphatidylinostitol) sugar phosphatidylinositol part 25 Molecular Cell Biology, 7th edition, Lodish et al. vSrc Ras and Rab  Structures of four common detergents Bile salt Denaturation of proteins Solubilizing integral membrane proteins 26 Molecular Cell Biology, 7th edition, Lodish et al.  Solubilization of integral membrane proteins by nonionic detergents 27 Figure 11-27 Essential Cell Biology (© Garland Science 2010)  Membrane disruption 28 Essential Cell Biology (© Garland Science 2010) Lodish  Berk  Kaiser  Krieger  scott  Bretscher  Ploegh  Matsudaira MOLECULAR CELL BIOLOGY SEVENTH EDITION CHAPTER 11 Transmembrane Transport of Ions and Small Molecules Copyright © 2013 by W. H. Freeman and Company  Cell membranes contain specialized membrane transport proteins 30 Figure 12-1 Essential Cell Biology (© Garland Science 2010)  Relative permeability of a pure phospholipid bilayer to various molecules and ions 31 Molecular Cell Biology, 7th edition, Lodish et al.  Table of content  Overview of transmembrane transport  Facilitated transport of glucose and water  ATP-powered pumps and the intracellular ionic environment  Nongated ion channels and the resting membrane potential  Cotransport by symporter and antipoters  Transcellular transport 32  Typical intracellular and extracellular ion concentrations 33 Table 12-1 Essential Cell Biology (© Garland Science 2010)  Electrochemical gradients (chemical) 34 Figure 12-7 Essential Cell Biology (© Garland Science 2010)  Overview of membrane transport proteins Three main classes of membrane proteins 1 2 3 cotransporters  1. Movement of specific ions (or water) down their electrochemical gradient. (passive transport or facilitated diffusion), facilitated transporter.  2A. Transport a molecule down its concentration gradient, facilitated transporter  2B. and C. Movement of one molecule against its concentration gradient (black), driven by the movement of one or more ions down an electrical gradient  3. Use energy to power the movement of specific ions or small molecules. Active transport 35 Molecular Cell Biology, 7th edition, Lodish et al.  Multiple membrane transport proteins function together in the plasma membrane of metazoan cells Create an electric potential Oppositely directed concentration gradients Na+ ion concentration gradient Membrane potential 36 Molecular Cell Biology, 7th edition, Lodish et al.  Mechanisms for transporting ions and small molecules across cell membranes Secondary active transport 37 Molecular Cell Biology, 7th edition, Lodish et al.  Table of content  Overview of transmembrane transport  Facilitated transport of glucose and water  ATP-powered pumps and the intracellular ionic environment  Nongated ion channels and the resting membrane potential  Cotransport by symporter and antipoters  Transcellular transport 38 Several features distinguish uniport from simple diffusion  The rate of substrate movement by uniporters is far higher than simple diffusion.  The solubility of the transported molecules in the lipid membrane is irrelevant.  There is a maximum transport rate, Vmax, which depends on the number of uniporters in the membrane.  Transport is reversible, and the direction of transport changes if the direction of the concentration gradient changes  Transport is specific. 39  Model of uniport transport by GLUT1  In the plasma membrane of most mammalian cells.  If glucose concentration is higher inside the cell than outside, the cycle will reverse.  Transcellular transport of glucose from the intestinal lumen into the blood. 40 Molecular Cell Biology, 7th edition, Lodish et al.  Osmotic pressure  Osmosis: movement of water from a region of low solute concentration to a region of high solute concentration.  Osmotic pressure: the driving force for the water movement is equivalent to a difference in water pressure.  The osmotic pressure is directly proportional to the difference in the concentrations of the total numbers of solute molecules.  For example, a 0.5 M NaCl solution is actually 0.5 M Na+ ions and 0.5 M Cl- ions and has a similar osmotic pressure as a 1 M solution of glucose or sucrose. 41 Molecular Cell Biology, 7th edition, Lodish et al.  The diffusion of water is known as osmosis 42 Figure 12-12 Essential Cell Biology (© Garland Science 2010)  Red blood cells 43 Essential Cell Biology (© Garland Science 2010)  Cells use different tactics to avoid osmotic swelling Na+-K+ pump  The cell walls resist the expansion of the volume of the cell.  The contractile vacuoles take up water from the cytosol and periodically discharge its contents through fusion with the plasma membrane. 44 Figure 12-13 Essential Cell Biology (© Garland Science 2010)  Water molecules diffuse rapidly through aquaporin channels tetramer water  Aquaporins are water-channel proteins that specifically increase the permeability of cellular membranes to water.  The formation of hydrogen bonds between the oxygen atom of water and the amino groups of two amino acid side chains ensures that only uncharged water passes through the channel.  Aquaporin 2 in the plasma membrane of certain kidney cells is essential for the resorption of water from urine being formed. 45 Figure 12-6 Essential Cell Biology Molecular Cell Biology, 7th edition, Lodish et al.  Expression of aquaporin by frog oocytes increases their permeability to water Microinjected with mRNA encoding aquaporin Control oocyte 46 Molecular Cell Biology, 7th edition, Lodish et al.  Table of content  Overview of transmembrane transport  Facilitated transport of glucose and water  ATP-powered pumps and the intracellular ionic environment  Nongated ion channels and the resting membrane potential  Cotransport by symporter and antipoters  Transcellular transport 47  ATP-powered pumps  Transport ions and various small molecules across membranes against their concentration gradients.  Transmembrane proteins with one or more binding sites for ATP located on subunits or segments of the protein that face the cytosol.  P, F, and V-class pumps transport only ions, as do some members of the ABC superfamily.  ABC superfamily can transport small molecules such as amino acids, sugars, peptides, lipids, and many types of drugs. 48  The four classes of ATP-powered transport proteins Phosphorylated Not phosphorylated 49 Molecular Cell Biology, 7th edition, Lodish et al.  P-class pumps 50 Molecular Cell Biology, 7th edition, Lodish et al.  Operational model of the Ca2+ ATPase in the SR membrane of skeletal muscle cells  Ca2+: Signaling pathways and muscle contraction  In skeletal muscle cells, Ca2+ ions are concentrated and stored in the SR.  The release of Ca2+ ions from the SR lumen into the cytosol causes muscle contraction.  The affinity of Ca2+ for the cytosolic-facing binding sites in E1 is 1000-fold greater than the other site. 51 Molecular Cell Biology, 7th edition, Lodish et al.  Operational model of the plasma membrane Na+/K+ ATPase 52 Molecular Cell Biology, 7th edition, Lodish et al.  Na+/K+ pump Essential Cell Biology (© Garland Science 2010) 53  V-class and F-class pumps  Transport only protons  V-class: Pumping protons against a concentration gradient (from the cytosolic to the exoplasmic face of the membrane)  F-class: Reverse proton pumps use the energy in a proton concentration of voltage gradient to synthesize ATP 54 Molecular Cell Biology, 7th edition, Lodish et al.  Effect of V-class H+ pumps on H+ concentration gradients and electric potential gradients across cellular  Proton pumping generates electric potential across the membrane No electric potential  Movement of an equal number of anions in the same direction  Movement of equal numbers of a different cation in the opposite direction 55 Molecular Cell Biology, 7th edition, Lodish et al.  ABC superfamily  Multidrug resistance protein in Two transmembrane domain cancer cells. Two cytosolic ATP binding domain  Localize in plasma membrane and the membranes of many intracellular organelles. 56 Molecular Cell Biology, 7th edition, Lodish et al.  Selected human ABC proteins 57 Molecular Cell Biology, 7th edition, Lodish et al.  Structure and function of the cystic fibrosis transmembrane regulator (CFTR)  Expressed in the apical plasma membranes of epithelial cells in the lung, sweat glands, pancreas, and other tissue.  A channel, not a pump  R domain is phosphorylated by cAMP- dependent protein kinase (PKA), followed by ATP binding to cytosolic A domain.  Most of the cystic fibrosis can be attributed to a single mutation in R domain A domain CFTR  Cystic fibrosis affects the cells that produce mucus, sweat, and digestive juices.  A defective gene causes the secretions to become sticky and thick. Instead of acting as lubricants, the secretions plug up tubes, ducts, and passageways. 58 Molecular Cell Biology, 7th edition, Lodish et al.  Table of content  Overview of transmembrane transport  Facilitated transport of glucose and water  ATP-powered pumps and the intracellular ionic environment  Nongated ion channels and the resting membrane potential  Cotransport by symporter and antipoters  Transcellular transport 59  Different types of gated ion channels respond to different types of stimuli Non-gated channel: The channel is always open, such as K+ channel and aquaporins. 60 Figure 12-26 Essential Cell Biology  Generation of a trans-membrane electric potential (voltage)  The plasma membrane of animal cells contain many open K+ channels but few open Na+, Cl-, or Ca2+ channels.  The major ionic movement across the plasma membrane is the movement of K+ from the inside outward. The movement leaves an excess of negative charge on the cytosolic face of the plasma membrane and creates an excess of positive charge on the exoplasmic face. Molecular Cell Biology, 7th edition, Lodish et al. 61  The electric potential across the plasma membrane of living cells can be measured 62 Molecular Cell Biology, 7th edition, Lodish et al.  Mechanism of ion selectivity and transport in resting K+ channels Carbonyl group  As K+ ions pass through the selective filter, they lose their bound water molecules and become bound instead to eight backbone carbonyl oxygen atoms that are part of the conserved amino acid sequence of the selective filter.  The smaller Na+ ion can’t bind perfectly to the channel oxygen atoms. 63 Molecular Cell Biology, 7th edition, Lodish et al.  Potassium channel 64 Essential Cell Biology (© Garland Science 2010)  Table of content  Overview of transmembrane transport  Facilitated transport of glucose and water  ATP-powered pumps and the intracellular ionic environment  Nongated ion channels and the resting membrane potential  Cotransport by symporter and antipoters  Transcellular transport 65  Transmembrane forces acting on Na+ ions  There are many types of Na+- linked symporters.  The inward movement of Na+ is thermodynamically favored. 66 Molecular Cell Biology, 7th edition, Lodish et al.  Operational model for the two-Na+/one- glucose symporter  Intestinal epithelial cells possess a glucose–Na+ symport, which they can use to take up glucose from the gut lumen, even when the concentration of glucose is higher in the cell’s cytosol than it is in the gut lumen.  Other Na+ -powered symporters: Na+/amino acid symporters, Na+/neurotransmitter symporters 67 Molecular Cell Biology, 7th edition, Lodish et al.  Glucose uptake 68 Essential Cell Biology (© Garland Science 2010)  Carbon dioxide transport in blood requires a Cl–/HCO3– antiporter  If anion exchange did not occur, HCO3- would accumulate inside the erythrocyte to a toxic level, as the cytosol would become alkaline.  80% of the CO2 in blood is transported as HCO3- generated inside erythrocytes. 69 Molecular Cell Biology, 7th edition, Lodish et al.  Table of content  Overview of transmembrane transport  Facilitated transport of glucose and water  ATP-powered pumps and the intracellular ionic environment  Nongated ion channels and the resting membrane potential  Cotransport by symporter and antipoters  Transcellular transport 70  Transcellular transport of glucose from the intestinal lumen into the blood Molecular Cell Biology, 7th edition, Lodish et al. 71  Acidification of the stomach lumen by parietal cells in the gastric lining P-lass H+/K+ pump Molecular Cell Biology, 7th edition, Lodish et al. 72  Dissolution of bone by polarized osteoclast cells requires a V-class proton pump and the ClC-7 chloride channel protein Molecular Cell Biology, 7th edition, Lodish et al. 73  Some examples of transmembrane pumps 74 Essential Cell Biology (© Garland Science 2010)