MnR S1 - Lipids, Proteins and Membrane Structure

Question 1

What are the main kinds of lipid found in biological membranes?

Answer 1

Phospholipid, sphingomyelin, glycolipid and cholesterol

Question 2

What are the main functions of a plasma membrane?

Answer 2

• Recognition
• Communication
• Control of enclosed chemical environment
• Highly selective permeability barrier
• Signal generation in response to stimuli

Question 3

How are lipids dynamic in the membrane?

Answer 3

• Flip flop
• Lateral diffusion
• Axial rotation
• Flexion

Question 4

List the general properties of fatty acids

Answer 4

• C16 and C18 most prevalent

- Unsaturated double bonds in cis arrangements creates a kink resulting in looser packing

Question 5

What is an amphipathic molecule?

Answer 5

Has both hydrophobic and hydrophilic moieties

Question 6

Outline the process of lipid bilayer formation

Answer 6

• Occurs spontaneously when phospholipids and glycolipids are placed in a aqueous medium
• Formation is driven by van der Waals forces and stabilised by electrostatic and hydrogen bonds

Question 7

Describe the differences between integral and peripheral proteins

Answer 7

Peripheral - bound to surface of membrane by electrostatic and ionic interactions. Removed by changes in pH or ionic strength

Integral - interact extensively with hydrophobic regions of membrane, removed by detergents that compete for non-polar interaction in the bilayer

Question 8

What is the importance of membrane asymmetry?

Answer 8

Asymmetrical orientation is important for protein function Eg receptors for hydrophilic extracellular messenger

Question 9

What is the effect of unsaturated fatty acids on membrane fluidity?

Answer 9

Less closer packing increases fluidity

Unsaturated hydrocarbons chains with cis double bonds reduce phospholipid packing

Question 10

What is the effect of cholesterol on membrane fluidity?

Answer 10

Polar head group hydrogen bonds to reduce chain motion reducing fluidity (high temps)

Rigid sterol ring prevents close packing increasing fluidity (low temps)

Question 11

Describe the fluid mosaic model of the plasma membrane

Answer 11

Biological membranes are composed of a lipid bilayer with associated membrane proteins which may be deeply embedded in the bilayer (integral) or associated with the surface (peripheral)

Question 12

How is protein movement restricted in the membrane?

Answer 12

Lipid mediated effects, membrane protein association and association with extra-membranous proteins

Interaction with cytoskeleton prevents lateral movement

Question 13

What is the evidence for membrane proteins?

Answer 13

Ion gradients, facilitated diffusion and specificity of reactions

Question 14

In what way do membrane proteins move?

Answer 14

Conformational change, rotational and lateral

NO FLIP FLOP - as they have large hydrophilic moieties that would require a large amount of energy for them to pass through the hydrophobic region of the bilayer

Question 15

How do membrane proteins contribute to the cytoskeleton? Eg Erythrocytes

Answer 15

• Network of spectrin and actin molecules
• Alpha and beta sub-units wind together to form anti-parallel heterodimer
• Two heterodimers go head to head to form heterotrimer joined by actin protofilaments, band 4.1 and adducing molecules
• Ankyrin links spectrum and band 3
• Band 4.1 links glycophorin A

Question 16

How do membrane proteins insert themselves into the membrane?

Answer 16

• Passage of the protein through the membrane must be arrested
• The stop transfer signal is a region of highly hydrophobic primary sequence of between 18 and 22 amino acids long followed directly by charged amino acids
• This is long enough to span the hydrophobic core of the bilayer forming the transmembranous region of the protein

Question 17

How are multiple transmembrane domains formed?

Answer 17

• Folding of the nascent protein against the constraint of the first transmembrane segment is the driving force for the insertion of the other domains
• It is possible that a series of start and stop transfer sequences within the primary structure control membrane insertion
• The association of lumens binding proteins related to the family of heat-shock proteins also assist in stabilising the partially folded growing polypeptide

Question 18

Give two examples of haemolytic anaemias

Answer 18

Hereditary spherocytosis - spectrum levels may be depleted. 40-50% of cells round up and become much less resistant to lysis during passage through the capillaries and are cleared by the spleen shortened in vivo survival of red blood cells and the inability of the bone marrow to compensate for their reduced life span leads to haemolytic anaemia

Hereditary elliptocytosis - a common defect in a spectrum molecule that is unable to form heterotetramers resulting in fragile elliptoid cells

Question 19

What is unique about sphingomyelin?

Answer 19

The only phospholipid not based on glycerol

Question 20

What is the difference between a cerebroside and ganglioside?

Answer 20

Botha are sugar containing lipids but:

Cerebrosides head group sugar is a monomer whilst a ganglioside head group sugar is a oligosaccharide

Question 21

Outline the secretory protein synthesis pathway

Answer 21

• Free ribosome initiates protein synthesis from mRNA molecule
• Hydrophobic N-terminal signal sequence is produced.
• Signal sequence of newly formed protein is recognised and bound to by the signal recognition particle (SRP)
• Protein synthesis stops
• GTP-bound SRP directs the ribosome synthesising the secretory protein to SRP receptors on the cytosolic face of the ER
• SRP dissociates
• Protein synthesis continues and the newly formed polypeptide is fed into the ER via a pore in the membrane (peptide translocation complex).
• Signal sequence is removed by a signal peptidase once the entire protein has been synthesised
• The ribosome dissociates and is recycled

Question 22

What is a hydropathy plot used for?

Answer 22

Determines how many transmembrane region a protein has