Session 1 Flashcards
Describe the composition of biological membranes
60% protein
40% lipid
1-10% carbohydrate
Describe the main functions of biological membranes
Selective permeability barrier, control of chemical environment, communication, recognition of different molecules (signalling, immune), signal generation in response to stimuli
Describe the properties of a fluid membrane
Amphipathic molecules, phospholipids, sphingomyelin (not based on glycerol), glycolipids (cerebroside, ganglioside), cholesterol
Describe the contribution of cholesterol to membrane stability
High temperatures - forms hydrogen bonds with the double bonded oxygen atoms in the ester bond of phospholipid molecules via its hydroxyl group - reduces fluidity and phospholipid fatty acid tail mobility
Low temperatures - intercalates with phospholipid molecules and reduces their ability to form ordered packed crystals - increases membrane fluidity
Outline the evidence for membrane proteins
Biochemical - membrane fractionation + gel electrophoresis, freeze fracture
Functional - different functions indicate presence e.g. facilitated diffusion, ion gradients, specificity
Describe how membrane proteins associate with the lipid bilayer
Peripheral - bound to surface via electrostatic attractions, H bond and disulphide bonds, removed by changes in pH or ionic strength
Integral - interact with hydrophobic domains of membrane, removed by detergents and organic solvents that compete for non-polar interactions, may be transmembranous
Describe how membrane proteins may move
Conformational change, rotational, lateral diffusion.
(Restriction on mobility: aggregates, lipid mediated effects, associations with extra membranous proteins, interactions with other cells)
Describe how membrane proteins contribute to the cytoskeleton
Erythrocyte cytoskeleton is a network of spectrin and actin molecules - form a heterotetrameter of a2B2.
Band 4.1 and adducin molecules form interactions towards the ends of the spectrin rods.
The spectrin-actin network is attached to the membrane through adapter proteins. Ankyrin (band 4.9) links band 3 and band 4.1 links Glycophorin A.
Attachment of integral membrane proteins to the cytoskeleton restricts the lateral mobility of the membrane protein
Explain Hereditary Spherocytosis
Spectrin levels are depleted by up to 50%, cells round up and become less resistant to lysis during passage through capillaries and are cleared by spleen –> haemolytic anaemia. (Treatment - transfusions)
Explain Hereditary Elliptocytosis
Mutation in spectrin prevents end-to-end associations, unable to form heterotetrameters, become fragile and elliptoid shaped –> haemolytic anaemia. (Treatment - cytochalasin drugs - cap growing end of polymerising actin filaments)
Describe how membrane proteins are inserted into membranes
Signal sequence is recognised by SRP.
Binding of SRP locks ribosome complex and prevents further protein synthesis while ribosome is still in cytoplasm.
On the ER, SRP is recognised by SRP receptor (docking protein) and SRP is released from signal sequence, removing the inhibition of further translation.
Signal sequence interacts with signal sequence receptor (SSR) within a protein translocator complex (Sec61) which directs further synthesis through ER membrane.
The ribosome becomes anchored to the complex.
The stop transfer signal, in a-helical form stops the passage of the protein through the membrane.
The result is a transmembranous protein with its N-terminal directed into the lumen and it’s C-terminal into the cytoplasm
Discuss how the correct orientation of membrane proteins is achieved
Membrane protein topology is important for function and leads to asymmetrical orientation.
The positioning of positively charged residues defines their orientation.
Positively charged residues at N terminal end = C terminal section passes into lumen
Positively charged residues at C terminal end = N terminal section passes into lumen
