1. AH Biology: Unit 1 Cells and Proteins Membrane Proteins: Overview

2. Plasma membrane The plasma membrane consists mainly of a fluid mosaic bilayer of phospholipids and protein. Phospholipids will naturally form bilayers in aqueous environments because of their amphipathic nature. Hydrophilic head groups align to the extracellular space or cytoplasm, and the hydrophobic tails point inwards.

3. Membrane structure Fluid mosaic model showing major membrane components.

4. Membrane proteins The three major roles of membrane proteins are: movement of molecules across membranes transmission of extracellular signals, ie signal transduction detecting and amplifying stimuli: photoreceptor protein systems.

5. Movement of molecules across membranes Synthetic bilayers can be constructed to study membrane permeability. –Hydrophobic molecules such as O 2, CO 2, N 2 and steroid hormones pass readily across such bilayers –Small uncharged polar molecules (eg H 2 O, urea and glycerol) pass through readily but at a lower rate as they are capable of dissolving in the bilayer. –Large uncharged polar molecues (eg glucose and sucrose) cannot pass through. –Protein-free bilayers are impervious to all ions, eg H +, Mg 2+, Ca 2+ and HCO 3 –.

6. Movement of molecules across membranes The smaller and less hydrophilic a molecule is the easier it can pass through the lipid phase of the bilayer. This leaves a conundrum as large, charged and hydrophilic molecules clearly are transported across cell membranes. Membrane transport proteins facilitate such transfers.

7. Membrane transport proteins All membrane transport proteins have been shown to have parts of their structure which pass multiple times across the bilayer, forming continuous protein pathways. Most are arrangements of alpha- helixes although folded beta-sheets, the so-called beta-barrel, have also been known to form pores and channels. Proteins that span the membrane are called transmembrane proteins.

8. Membrane transport proteins Two main classes of transport proteins exist: –Channels Transport is always passive. Solute passage can be gated or ungated. Gated channels can selectively allow passive transport by altering their conformation to ligand binding (ligand-gated) or changes in ion concentration (voltage-gated). –Transporters Transport solutes passively with the concentration or electrochemical gradient, ie facilitated diffusion. Transport solutes against the concentration or electrochemical gradient, ie active transport. Such transport requires energy.

9. Membrane transport proteins Protein Phospholipid

10. Membrane transport proteins Where the concentration gradient combines with the charge on molecules an electrochemical gradient can build up. The charge on the membrane surfaces can create a membrane potential, which aids (right) or hinders (middle) transport. + + + + + + + + + + ++ +++ + -- --- - + + + + + -- --- - ++ +++ + Electrochemical gradient with no membrane potential Electrochemical gradient from outside to in: membrane potential +ve inside Electrochemical gradient from outside to in: membrane potential -ve inside

11. Specialisation of function Transport proteins: –Decrease the pH of endomembranes compartments such as the lysosome and endosome. Specific proton pumps pump H + into the structure to acidify the lumen. Such organelles lack the Na + pumps found in the plasma membrane. –E. coli bacteria contain a lactose permease. This transporter transports extracellular lactose into the cell. –The distribution of specific transporters can be non-uniform. Intestinal cells may have glucose transporters specifically on the lumen and basal sides but not on their lateral junctions; this arrangement promotes transport of glucose from the lumen across the intestinal wall.

12. Specialisation of function Channel proteins can: –increase bulk flow of water across the plasma membrane, eg aquaporins, which allow water flow but are impermeable to ions –regulate Na + and K + flow through dedicated channels, which can allow or shut down diffusion –exist as ion-gated channels at muscle synapses which open on reacting to neurotransmitters, resulting in a change of membrane potential and generating a potential difference. The chemical signal generates an electrical one, which passes along the nerve.

13. Signal transduction Where extracellular messages are hydrophilic, eg protein hormones such as STH (human growth hormone) and insulin or neurotransmitters such as acetlycholine, they are unable to pass directly through the lipid bilayer. They are not directly transported across membranes instead their message is transduced, ie converted into an intracellular signal by the act of binding to target receptors in the plasma membrane. This may activate enzymes, alter uptake or secretion of molecules, regulate gene transcription or rearrange the cytoskeleton. Many target receptor proteins are glycoproteins, ie proteins with sugar groups bound to them.

14. Photoreceptor protein systems These proteins are found across the three domains: archaea, prokaryotes and eukaryotes. Three of the best characterised systems are the following: –Bacteriorhodopsin is a protein used by archaea. It is a light-coupled proton pump that pumps protons out of the cell. The resulting back diffusion of H + drives ATP synthase and generates ATP. –Photophosphorylation in plants. Photosynthetic pigments on the thylakoid drives ion flow, resulting in the pumping of H + across the membrane. The resulting back diffusion of H + drives ATP synthase and generates ATP. –Rhodopsin. A combination of the membrane protein opsin and its co-factor retinal is found in the retina of animals. This is an example of light-generated signal transduction resulting in a specific activation of an enzyme. Sufficient formation of product intracellularly may generate a nerve impulse.