Lecture 9: Membranes as borderlines - 1 Flashcards
What is the most abundant type of lipid in the membranes of our cells?
Phospholipids
Describe the structure of a phospholipid.
Phospholipids are composed of a hydrophilic head and a hydrophobic tail.
- The hydrophilic head is composed of a glycerol headgroup that is connected to a phosphate group. The phosphate group is able to bind to another head group, e.g. choline.
- The hydrophobic tail is composed of two fatty acid tails. One tail is often unsaturated, which influences the packing and the rigidity of the membrane.
Don’t learn by heart, but just to clarify:
If one of the tails of the phospholipid is saturated, how does this effect the packing and the rigidity of the membrane? And vice versa how does an unsaturated fatty acid affect the packing and rigidity of the membrane?
- Saturated fatty acids press in on each other, making a dense and fairly rigid membrane.
- Unsaturated fatty acids have ‘kinks’ in their tails, which push adjacent phospholipid molecules away. Making the membrane more fluid.
Name the 3 main phospholipids and 2 main sphingolipids. Also describe some characteristics of these lipids.
The main lipids are: phosphatidylethanolamine, phosphatidylserine, phosphatidylcholine, sphingomyelin and sphingosine.
- The phosphatidyl lipids are composed of: 2 fatty acid tails that are connected to the glycerol backbone. The glycerol backbone is bound to a phosphate group. The ethanolamine, serine and choline are the head groups that are bound to the phosphate groups. (Note: serine is negatively charged).
- The sphingolipids are different in the way that they have only one fatty acid tail or/and only a fatty chain, that they contain extra hydroxyl groups (makes the lipid more hydrophillic) and the fact that they don’t have a glycerol backbone.
Describe the characteristics of cholesterol.
Cholesterol is not a lipid, but it is part of the membrane in quite some abundance. Cholesterol provides rigidity to the membrane by intercalating between two phospholipids.
The lipid composition differs in different cell type membranes. But what are the most abundant lipids?
Cholesterol and the phospholipids.
The (spontaneous) packing of phospholipids in aqueous solution depends on the shape of the lipid. How are phospholipids packaged when they’re single-tailed and how are they packaged when they’re double-tailed?
- Single-tailed → micelle
- Double-tailed → lipid bilayer
Explain why this shape of a lipid bilayer is energetically unfavorable.
Because the edges of the bilayer (the acyl chaines) are still exposed to water.
What shape of a lipid bilayer is energetically favorable?
The shape of a liposome (sealed compartment formed by phospholipid bilayer), so that there’s no connection between the water and the acyl chains.
The bilayer is fluid/bendable.
Describe how different parts of the lipid bilayer can move.
- There can be rapid lateral diffusion of the lipid bilayer, from right to left and vice versa.
- A phospholipid can also flip from one side of the lipid bilayer to the other side, but this is energetically unfavorable and goes much slower. (This is due to the fact that the hydrophilic headgroup needs to move across the hydrophobic tails).
What factors influence the fluidity of the membrane?
Temperature and membrane composition.
- Lower temperature → less fluidity
- High concentration of saturated lipid and high concentration of cholesterol → less fluidity
What is meant by the fact that lipid bilayers are not homogeneous and that rafts may be able to form?
That the lipid bilayer needs to be dynamic for different processes. E.g. in the case of exocytosis of a vesicle, where the process of exocytosis needs certain proteins and lipids on the membrane. So these proteins/lipids are then recruited into rafts (dense places on the membrane).
Just study.
An example of a raft that is composed of different lipids and certain proteins.
Ok
Why is it important that bilayers are asymmetric in composition?
It’s important for membrane function, e.g. binding of specific proteins to specific lipids (important for signaling).
Name examples of specific lipids in the asymmetric bilayer and also name their function.
- Phosphatidylinositol is exclusively located in the cytosolic leaflet, it can bind cytosolic proteins upon activation by phosphorylation.
- Phosphatidylserine is a negatively charged phospholipid, recruits positively charged proteins.
- Glycolipids are exclusively located in the outer layer, important for protection of the membrane, electrical effects (ionic concentration) and cell recognition.
What can also happen to these specific phospholipids in the membrane?
Bacterial toxins can bind to them to e.g. enter the cell.
Just study.
Ok
Most transmembrane segments are a-helical. Describe what this means.
- The helix maximizes internal hydrogen bonding between peptide bonds to reduce free energy.
- This can be single or multipass.
- It connects functional domains at two sites of the membrane.
- It often interacts with other transmembrane segments, even in other proteins.
- The helix is generally hydrophobic or slightly amphiphilic and around 20 aa long! Therefore, it can be screened for in whole genomes.
- What is a hydropathy plot?
- What is the hydropathy index?
- A hydropathy plot is the analysis of the degree of hydrophobicity or hydrophilicity of amino acids of a protein. It is used to characterize or identify possible structures or domains of a protein.
- The hydropathy index of an amino acid is a number representing the hydrophobic or hydrophilic properties of its sidechain. The larger the number is, the more hydrophobic the amino acid.
What can you conclude with the help of a hydropathy plot?
If it’s a membrane protein → how the protein is integrated in the membrane.
On the picture you can see that glycophorin has one hydrophobic domain, which probably means it only crosses the membrane once. On the other hand, bacteriorhodopsin has several hydrophobic domains, which would indicate that it’s an integral membrane protein that crosses the membrane several times (like a beta-barrel).
Describe the compaction and folding of a newly synthesized multipass transmembrane protein.
- First, there’s insertion of individual transmembrane segments in the lipid bilayer.
- After this, the individual transmembrane segments will interact and come closer with each other.
Describe this membrane protein (pyrophosphatase) that is depicted in the picture.
This is a pyrophosphatase, a dimer that works as a proton pump. It is only present in plants and bacteria and can thus be used as a drug target.
- The hydrophobic alpha helixes and the hydrophilic part of the protein are visible. You can also see that the two protein are interacting with the lipids, but that they’re also bound to each other.
Describe this membrane protein (Mechanosensitive channel) that is depicted in the picture.
This protein consists of 7 subunits (homoheptamer) and contains three transmembrane segments per subunit. It is highly dynamic and responds to mechanic stress to allow efflux of water and solutes.
As depicted in the picture, this protein has two different structures → closed and open.
Why is it difficult to determine the structure of a membrane protein?
For analysis of the membrane protein, the membrane first needs to be dissolved. During this process, the native structure of the protein is lost and also does not behave the same without its normal environment (the lipid bilayer).
