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Download LECTURES 5, 6 Membrane protein lecture
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Membrane Proteins Membrane Proteins Protein structure • Primary structure Amino acids: Polar (charged and uncharged) Non polar Unique side chains (Gly, Cys, Pro) • Secondary structure • Tertiary structure • Quaternary Polar amino acids * Serine * Threonine Side chains have partial charge ∴ participate in reactions, associate with water Glutamine * Tyrosine Asparagine Non-polar amino acids Alanine Valine Leucine Side chains have H and C atoms; hydrophobic Isoleucine Associate with lipid layer Methionine Phenylalanine Tryptophan Amino acids with unique side chains Glycine (H side chain – hydrophobic or hydrophilic Cysteine (contains SH moiety – can form S-S bridge) Proline (hydrophobic side chain; can create kinks and disrupt 2° structure Secondary structure: α-helix Opposite sides of helix may have contrasting properties -hydrophobic -hydrophilic Secondary structure: β-sheet Bonds which maintain protein structure Tertiary structure • Stabilized by non covalent bonds between diverse chains of protein Some tertiary structures Haemoglobin has a quaternary structure: 2 α-subunits and 2 β-subunits Quaternary structure enhances O2 association Proteins in membrane 1. Receptors: specificity, subtypes 2. Ion channels: specificity, selectivity importance of pore size, and charge 3. Ion pumps 4. Enzymes: mainly on intracellular face 5. GTP-binding proteins 6. Carrier molecules: very specific 7. Cell adhesion molecules (Glycoproteins) MEMBRANE PROTEINS…… Communication Receptors Transport: Ion channels Pumps Carrier proteins Release: Synaptic plasma membrane proteins Integral membrane protein Single/several hydrophobic domain e.g. glycophorin/channels+pumps Peripheral: anchored by glycolipid e.g. Receptor Anchored to lipid bilayer eg G-prot Membranes as Barriers • Hydrophobic interior of bilayer is a barrier to transport (size & charge) • The membrane is impermeable to ions and large charged molecules and requires the aforementioned special membrane proteins to transport across Membrane proteins - NOTES Transmembrane proteins • Protein has hydrophilic and hydrophobic portions – Hydrophilic will interact with the aqueous solutions on either surface – Hydrophobic will be in contact with the hydrophobic interior of the bilayer • Also called integral membrane proteins Peripheral membrane proteins • Are attached to either surface of the bilayer • Those attached to lipids are covalently linked • Those that interact with other transmembrane proteins are attached by noncovalent interactions, such as: – H-bonds, hydrophobic and hydrophilic interactions Membrane-spanning proteins • Must have hydrophobic side chains in the area that spans the membrane • Peptide backbone is polar – Not “happy” in the hydrophobic interior Membrane Pores • When proteins span the membrane several times they usually form pores that allows molecules to move back and forth through the membrane • Multiple α helices span membranes – Hydrophilic on the inside of the channel – Hydrophobic on the outer surface of the channel α-Helix Span Interior (Pore) • Interior forces the peptide backbone to form α helix • Non-polar R groups are on the outside of the helix • Transmembrane proteins usually span the membrane once – Receptors – collect signal, pass on to the inside of cell β Barrel Pore • β barrels are made of β sheets that are curved into a cylinder • The hydrophilic line the inner side and hydrophobic the outer surface • Larger pore than α helix pore Membrane Transport of Small Molecules Membranes present a barrier to the movement of most materials Transport proteins allow movement Transport proteins comprise 15-30% of membrane proteins. Up to 2/3 of a cell’s metabolic energy can be used for transport Tight Junctions restrict transport Proteins can diffuse within their own domains, but are prevented from entering the other domain by ‘tight junctions’ (specialized cell junction) Transport 1. Simple Diffusion 2. Carrier-mediated (a) Facilitated diffusion High------Low (b) Active transport (ATP) Low High Uniport, symport antiport Primary, secondary Transport May be Passive or Active Passive transport may or may not require protein transporters; active transport always requires transporter proteins. The Electrochemical Gradient is the Determining Force for Ion Transport The electrochemical gradient is the combination of concentration and charge differences across the membrane. Carrier Proteins Bind Solutes Tightly and Undergo Large Conformational Changes The tightness and specificity of carrier protein-solute binding is much like enzyme-substrate binding. Protein phosphorylation changes conformation ATP + ADP Transport Via Carrier Proteins is Saturable Simple Diffusion is Not Active Transport Always Occurs Using Carrier Proteins (not channels) Coupled Carriers Function as Symports or Antiports Coupled carriers always function in active transport; uniports function in facilitated diffusion. A Glucose Antiport Driven by the Na+ Electrochemical Gradient The Na+ electrochemical gradient is harnessed to drive many transport processes. The Na+-K+ Pump is Abundant and Ubiquitous The Na+-K+ pump maintains low ic [Na+] and high ic [K+] Ionic imbalance important for intracellular pH control, osmotic control, excitability, and transport The Na+-K+ Pump is a P-Type Transport ATPase This class of pumps autophosphorylates following ATP hydrolysis. The phosphorylation is reversible and changes the conformation of the pump, alternately exposing ion binding sites on the extracelluar and cytosolic faces of the membrane. About 1/3 of the Cell’s Metabolic Energy Goes to Powering the Na+-K+ Pump The Na+-K+ Pump The Na+-K+ Pump is abundant and ubiquitous The Na+-K+ pump maintains low ic [Na+] and high ic [K+] It is actually an enzyme – ATPase (P-type transport ATPase) The phosphorylation changes the conformation of the pump. Ionic imbalance important for intracellular pH control osmotic control excitability transport About 1/3 of the Cell’s Metabolic Energy Goes to Powering the Na+-K+ Pump Vesicular Transport • Transport of large particles and macromolecules across plasma membranes – Exocytosis – moves substance from the cell interior to the extracellular space – Endocytosis – enables large particles and macromolecules to enter the cell – Phagocytosis – pseudopods engulf solids and bring them into the cell’s interior Vesicular Transport Endocytosis of cholesterol molecule (large) Clathrin-Mediated Endocytosis Figure 3.13 Exocytosis Figure 3.12a Ion Channels Ion Channels are the Second Major Class of Transport Proteins Ion channels differ from carriers in always working in passive transport, their exquisite selectivity, and their higher rate of transport. A single ion channel may transport up to 100 million ions per second, a rate 100,000 times higher than the fastest carrier. Ion channels are on all cells, but reach their highest level of sophistication on electrically excitable cells like neurons. Channel Opening and Closing is Regulated in Three Broad Ways Receptors SIGNALLING THROUGH 1. Ionotropic receptors 2. Metabotropic receptors/G-protein-linked 3. Tyrosine kinase-linked receptors 4. Cytokine receptors (Class I and II) 5. Tumour necrosis factor (TNF) family 6. Haematopoietic antigen receptors Ionotrophic Receptors G-protein-linked receptors G-protein-linked receptors Tyrosine kinase receptors Note steps involved: 1. Ligand Reception 2. Receptor Dimerization 3. Catalysis (Phosphorylization) 4. Subsequent Protein Activation 5. Further Transduction 6. Response