Lecture 1 - Lipids, Proteins and Membrane Structure Flashcards

1
Q

What does amphipathic mean?

A

Contains both hydrophilic and hydrophobic parts.

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2
Q

What is the dry weight composition of a membrane?

A

40% lipid
60% protein
1-10% carbohydrate

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3
Q

What are the components of a phospholipid?

A

Glycerol
Phosphate head group
Fatty acid chains

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4
Q

How do unsaturated fatty acid side chains reduce phospholipid packing?

A

Introduce a kink in the chain.

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5
Q

What is sphingomyelin?

A

The only phospholipid not based on glycerol - conformation resembles a phospholipid.

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6
Q

What is a glycolipid?

A

Sugar containing lipid.

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7
Q

What is a cerebroside?

A

Glycolipid where the head group is a sugar monomer.

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8
Q

What is a ganglioside?

A

Glycolipid where the head group is a sugar oligosaccharide.

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9
Q

What is cholesterol?

A

Plasma membrane lipid.

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10
Q

What can amphipathic molecules form in water?

A

MicellesBilayers

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11
Q

What drives bilayer formation?

A

Spontaneous - driven by Van der Waals forces between hydrophobic tails.

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12
Q

How can lipid molecules move in lipid bilayers?

A

Intra chain motion - kink formation in fatty acyl chains
Fast axial rotation
Fast lateral diffusion - within the plane of the bilayer
Flip flop - movement of molecules from one half of the bilayer to the other - one for one exchange

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13
Q

What are 6 functions of membrane proteins?

A
Enzymes
Transporters
Pumps
Ion channels
Receptors
Energy transducers
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14
Q

How does protein content of the membrane vary?

A

18%-75%

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15
Q

What is the functional evidence for membrane proteins?

A

Facilitated diffusion
Ion gradients
Specificity of cell responses

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16
Q

What is the biochemical evidence for membrane proteins?

A

Membrane fractionation and gel electrophoresis

Freeze fracture

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17
Q

How can proteins move in the membrane?

A

Conformational change
Rotation
Lateral movement

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18
Q

Why can’t membrane proteins flip flop?

A

Large hydrophilic regions - large amounts of energy required to pass through the hydrophobic region of the bilayer.

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19
Q

What restricts the mobility of membrane proteins?

A

Lipid mediated effects - proteins separate into fluid phase or cholesterol poor regions
Membrane protein associations
Association with extra-membranous proteins

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20
Q

How are peripheral membrane proteins bound to the membrane surface?

A

Electrostatic bonds

Hydrogen bonds

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21
Q

How are peripheral membrane proteins removed?

A

Changes in pH

Changes in ionic strength

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22
Q

How do integral membrane proteins interact?

A

Interact with hydrophobic regions of bilayer.

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23
Q

How are integral membrane proteins removed?

A

Require agents eg detergents or organic solvents which compete for non polar interactions in bilayer - NOT pH or ionic strength.

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24
Q

Describe the protein secretion pathway.

A
  1. Free ribosome initiates protein synthesis from mRNA molecule.
  2. Hydrophobic N terminal signal sequence is produced.
  3. Signal sequence of newly formed protein is recognised and bound to by the signal recognition particle (SRP).
  4. Protein synthesis stops.
  5. GTP-bound SRP directs the ribosome synthesising the secretory protein to SRP receptors on the cytosolic face of ER.
  6. SRP dissociates.
  7. Protein synthesis continues and the newly formed polypeptide is fed into the ER via a pore in the membrane (peptide translocation complex).
  8. Signal sequence is removed by a signal peptidase.
  9. Ribosome dissociates and is recycled.
25
What is the purpose of a stop transfer signal?
To make sure membrane proteins span the membrane of a vesicle instead of being contained within it.
26
How does a stop transfer signal work?
18-20 amino acids long (distance to span bilayer) STS stays in the ER membrane Rest of protein is translated outside the ER in the cytoplasm
27
What are transmembrane regions made of?
Hydrophobic, small or polar uncharged amino acids.
28
What is a hydropathy plot used for?
To see how many transmembrane regions a protein has.
29
What is the importance of asymmetrical orientation of proteins in biological membranes?
Function eg receptor for hydrophilic extracellular messenger molecule must have recognition site directed towards extracellular space.
30
How does cholesterol increase membrane fluidity?
Reduces phospholipid packing.
31
How does cholesterol decrease membrane fluidity?
Reduces phospholipid chain motion.
32
Why is the plasma membrane described as fluid mosaic?
Fluid - hydrophobic integral components move laterally through the membrane Mosaic - made of many different parts
33
How does size affect the lateral diffusion of proteins in the membrane?
Membrane protein association Extramembranous intracellular protein associations Extracellular protein associations
34
How do lipid mediated effects affect the lateral diffusion of proteins in the membrane?
Proteins tend to separate into the fluid phase or cholesterol poor regions.
35
What molecules compose the erythrocyte cytoskeleton?
Actin | Spectrin
36
How is the erythrocyte cytoskeleton attached to the membrane?
Ankyrin and glycophorin adapter proteins.
37
What does ankyrin bind to?
Band 3.
38
What does glycophorin bind to?
Band 4.1
39
What effect does the attachment of integral membrane proteins to the cytoskeleton have?
Restricts lateral mobility of membrane proteins.
40
What happens if there is no erythrocyte cytoskeleton?
RBC round up - become more spherical RBC are lysed by shearing forces in capillary beds Cleared by spleen
41
What happens in hereditary spherocytosis?
``` Spectrin levels are depleted by 40%-50% Rounding up Increased lysis Reduced lifespan of RBC Bone marrow is unable to compensate Leads to haemolytic anaemia ```
42
What happens in hereditary ellipocytosis?
Spectrin molecules can't form heterotetramers Fragile elliptoid cells Leads to haemolytic anaemia
43
What are 5 general functions of biological membranes?
1. Continuous highly selective permeability barrier 2. Control of enclosed chemical environment 3. Communication 4. Recognition 5. Signal generation in response to stimuli
44
What are 4 types of phospholipid polar head group?
Choline, amines, amino acids, sugars
45
How much of the membrane lipid does cholesterol make up?
45%
46
What drives bilayer formation in water?
Van der Waals forces between hydrophobic tails
47
What stabilises the lipid bilayer?
Non covalent forces Electrostatic and hydrogen bonding between hydrophilic regions Interactions between hydrophilic groups and water
48
How do unsaturated double bonds in fatty acid side chains increase membrane fluidity?
Disrupt the hexagonal packing of phospholipids
49
What are biological membranes composed of?
Lipid bilayer | Associated membrane proteins
50
What are the two types of associated membrane proteins?
Integral and peripheral
51
What is an integral membrane protein?
Deeply embedded in the bilayer
52
What is a peripheral membrane protein?
Associated with the surface
53
How are erythrocyte ghosts prepared?
By osmotic haemolysis to release cytoplasmic contents
54
Which protein bands on the erythrocyte membrane are integral?
3 and 7
55
What sort of proteins are bands 3 and 7?
Glycoproteins
56
What is spectrin?
A long, floppy rod like molecule
57
What is the role of a and B subunits?
Wind together to form an antiparallel heterodimer. | Two heterodimers form a head-head association to form a hetertetramer of a2B2.
58
In a protein with multiple transmembrane domains, what is the driving force for the insertion of the domains?
The folding of the protein against the constraint of the first transmembrane segment