Lecture 11 - Membrane Receptors Cell membranes - Cellular membranes consist of a bilayer of phospholipid & cholesterol - Separates exterior from cytosol - This functions to: o Block passage of ions, proteins and other macromolecules o Enables membrane potential o Anchors proteins - Provide a 'relay' point for messages from outside cells to within cells (amplification) - Phospholipids comprise a range of polar head groups and two hydrophobic (fatty acid) tails Phospholipid in membrane - Phospholipid consist of different head groups and different fatty acid tails Structure: FA chain ff glycerol ffphosphate ff head group - Fatty acids: o Usually even number carbons (14-24 C) o Saturated (usually sn1) o Unsaturated (usually sn2) 606060 8060606 C 00000000 C Glycerol phospholipid + head group Cholesterol - Contains core 4-ringed isoprenoid hydrocarbon structure - Amphipathic due to key hydroxyl group o Different polarity on different sides of the membrane I- > hydrophilic and hydrophobic parts - Positioned between phospholipids within membranes ff increase membrane fluidity Different proteins within membranes - Categorised using : 1. Type of association: - Transmembrane - integral - Embedded - integral - Membrane associated (anchored) - Peripheral 2. Localisation - Extracellular - Intracellular 3. Function Plasma membrane H H HO Exoplasm Cytosol Lipid-anchored protein Integral membrane protein Peripheral membrane protein Hydrophilic phospholipid head group Phospholipid bilayer Hydrophobic fatty acyl side chains Peripheral membrane protein Cytoskeleton
Membrane Protein - Receptors often membrane bound - Act through several mechanisms: - Ion channel o Often activated through ligand binding -> causes conformational change of ion channel - Enzymatic o Enzyme linked receptors o Ligand (signal) will bind to inactive enzyme > activation -> product made - G protein linked o - Receptors may also be intracellular o In the nuclear cortex > below the phospholipid bilayer o Activated receptor could regulate transcription Trans - membrane proteins Characteristics: - Transmembrane region made of hydrophobic amino acid chain o Often contain a helices - Transmembrane region often highly conserved due to key catalytic role - Mainly function as channels or receptors to transfer extracellular signal to intracellular cascade How to identify a transmembrane protein: Hydrophobicity plots - Hydrophobicity plots are based upon the aqueous solubility of a region of amino acids - Hydrophobic sequences are less stable in aqueous environment, so tend to form stable intra membrane regions - Hydrophobicity can be calculated enabling a likelihood estimation of intra-membrane localisation Key: - Any region on the graph that is highly hydrophobic is likely to show the presence of a transmembrane region C-terminus Cytosol B 2 N- 1 C Hydropathy Index 0 PP 1 2 5 A E Phospholipid bilayer G F -] Retinal pigment -2. D 0 50 100 150 200 250 300 350 400 450 Exterior Amino Acids N-terminus
Seven transmembrane receptors > also known as G Protein coupled receptors Characteristics - Large exterior region (normally N terminal) containing ligand binding site - Interior (C terminal) contains binding sites for signalling components (e.g. G proteins) - Active (conserved) region often found