Lipid Bilayer, Proteins and Membrane Structure Flashcards
Describe the composition of the plasma membrane
- 40% Lipid
- 60% Protein
- 1-10% Carbohydrate
- 20% Water (hydrated)
What components may be associated with the hydrophilic region of a phospholipid?
- Choline
- Amines
- Amino acids
- Sugars
What is the significance of unsaturated fatty acids in phospholipid molecules?
- Unsaturated fats have a DOUBLE C=C BOND which introduces a ‘kink’ in the fatty acid chain
- This REDUCES PACKING of phospholipids in the membrane to increase fluidity
Describe the general structure of phospholipids
- GLYCEROL backbone
- Fatty acid chains attached to C1 and C2
- Phosphate group attached to C3
What is ‘sphingomyelin’?
- Only phospholipid NOT BASED ON GLYCEROL
- Resembles other phospholipids in the membrane
Describe the different types of glycolipids found in the membrane
- CEREBROSIDES - head group contains a SINGLE sugar monomer
- GANGLIOSIDES - head group contains many sugar OLIGOSACCHARIDES
What is a ‘glycolipid’?
Lipids with a carbohydrate attached by a glycosidic bond
What structure(s) can a lipid form in water?
MICELLE or BILAYER
Briefly describe the formation of a lipid bilayer in water
- Bilayer forms SPONTANEOUSLY in water by Van der Waals forces between the hydrophobic tails
- Cooperative structure is stabilised by NON COVALENT electrostatic forces and H bonding between the hydrophilic moieties and the polar heads with water
Name 4 ways in which lipids can move in the fluid bilayer
- FLEXION (intrachain motion)
- Fast axial ROTATION
- Fast LATERAL DIFFUSION within the plane of the bilayer
- FLIP FLOP
What is meant by lipids being able to ‘flip flop’ in the membrane?
Movement of lipid molecules from one half of the bilayer to the other on a one-for-one exchange basis
Why are there proteins embedded within the membrane?
- Proteins carry out a range of functions within the membrane - mainly SELECTIVE PERMEABILITY
- Can be transporters, enzymes, pumps, ion channels, receptors or energy transducers
What biochemical evidence is there for the existence of membrane proteins?
- Membrane fractionation and gel electrophoresis
- Freeze fracture
Describe the motion of membrane proteins within the membrane
- Conformational change (e.g. Receptors, carrier channels)
- Rotation
- Lateral diffusion within the bilayer
- NO FLIP FLOP
Why do membrane proteins not flip flop?
Contain LARGE HYDROPHILIC MOIETIES that would require a large amount of energy to pass through the hydrophobic region of the bilayer (would be THERMODYNAMICALLY UNSTABLE)
Describe 3 ways in which membrane protein movement is restricted
- AGGREGATES of membrane proteins in cholesterol-poor regions or due to lipid mediated effects
- INTERACTIONS WITH OTHER CELLS e.g. Synapses
- TETHERING extra-membranous association with peripheral proteins or cytoskeleton
What is the difference between peripheral and integral membrane proteins?
- PERIPHERAL - bound non-covalently to the surface by H bonds and electrostatic attractions
- INTEGRAL - interact extensively with hydrophobic regions of bilayer
How can integral proteins be removed from the bilayer?
- DETERGENTS or ORGANIC SOLVENTS
- Compete with proteins for the non polar interactions within the bilayer
Why are phospholipids described as ‘amphipathic’?
Contain both hydrophobic AND hydrophilic regions
How does cholesterol contribute to membrane stability at low and high temperatures?
- LOW - Reduces phospholipid packing to INCREASE fluidity
- HIGH - Reduces phospholipid chain motion to DECREASE fluidity
What are the restraints on mobility of proteins within the membrane?
- LIPID MEDIATED EFFECTS where proteins separate out in fluid phase or cholesterol poor regions
- MEMBRANE PROTEIN ASSOCIATIONS e.g. sugars
- ASSOCIATIONS WITH EXTRA-MEMBRANOUS PROTEINS (peripheral proteins e.g. cytoskeleton)
What is the percentage of protein in a lipid bilayer of an average cell?
~60% dry weight
Give 2 ways in which peripheral proteins can be removed
- Change in pH
- Change in ionic strength
Describe how integral proteins can be removed from the bilayer
- Detergents or organic solvents
- Compete for the non-polar interactions within the bilayer
Why is the asymmetric orientation of proteins important?
- RECEPTORS for hydrophilic messengers e.g. Insulin
- Recognition site must be directed towards extracellular space in order to detect signals
The majority of proteins within the erythrocyte membrane are peripheral. How do we know that they are on the cytoplasmic face?
The peripheral proteins are susceptible to proteolysis only when the cytoplasmic face is accessible
What are the only integral proteins in the erythrocyte membrane?
- BAND 3
- Glycophorin A (band 7)
What is the function of carbohydrate chains on membrane proteins?
- Extracellular carbohydrates are HIGHLY HYDROPHILIC
- Lock orientation of the protein and PREVENT FLIP-FLOP
- Role in cellular recognition
Describe the composition of the erythrocyte cytoskeleton
- Composed of SPECTRIN and ACTIN molecules
- Heterotetramers of spectrin are cross linked by short actin protofilaments
- Band 4.1 and Adductin form interactions towards the end of spectrin rods
Explain how erythrocyte membrane proteins associate with the cytoskeleton
- Attached by ADAPTOR PROTEINS
- Ankyrin (band 4.9) links spectrin to band 3 membrane protein
- Band 4.1 links spectrin to Glycophorin A
What two proteins link spectrin rods together in the cytoskeleton of RBC?
Adductin and Band 4.1
Describe the structure of spectrin
- α and β subunits wind together to form a HETERODIMER
- Two heterodimers form a head-to-head association forming a HETEROTETRAMER of α2β2
- Spectrin rods are cross linked by short actin protofilaments
What is the main role of the cytoplasm in erythrocytes?
Allows FLEXIBILITY and DEFORMABILITY of membrane so cells can pass through small capillaries without lysis
Describe how dominant hereditary spherocytosis can lead to haemolytic anaemia
- Autosomal dominant condition whereby spectrin levels of RBC are depleted by 40-50%
- Cells round up so cannot pass through capillaries, therefore undergo lysis in spleen
- Insufficient production of RBC by bone marrow leads to HAEMOLYTIC ANAEMIA
Explain the pathophysiology and treatment of hereditary elliptocytosis
- Genetic defect in spectrin so that it cannot form heterotetramers
- Results in fragile ellipsoid RBC
- Treated with CYTOCHALASIN drugs which can alter the deformability of RBC by capping polymerising actin filaments
Describe how membrane proteins are embedded in the ER membrane
- N terminal signal sequence recognised by SRP and binds to protein translocation complex on ER membrane
- Protein is threaded through membrane until a STOP TRANSFER SEQUENCE is reached (hydrophobic region of 18-22aa)
- STS spans the hydrophobic region of membrane and forms transmembraneous protein
How does the embedding of a transmembrane protein determine its orientation?
- Signal sequence on N terminus remains bound to PTC as protein is threaded through membrane
- Resulting orientation is N terminus on lumenal side and C terminus in cytoplasmic side
Give an example of a multiple spanning transmembrane protein
G protein coupled receptor
Describe how a transmembrane protein in the ER membrane is transported and embedded in the plasma membrane
- Transmembrane protein travels from ER to Golgi and is processed and packaged into vesicles
- Vesicles fuse with plasma membrane and embed protein in its correct orientation
