BIOL2200 Lecture Notes - Lecture 2: Phospholipid Scramblase, Biological Membrane, Prenylation

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30 Jun 2018
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Membranes lecture 2
Lipid mobility in phospholipid bilayers how they can move
Lipids have two main types of motion:
oSpinning without changing location not interesting or important
Rotation around their long axis
oLateral diffusion - movement with the same leaflet rapid
Phospholipids exchange position with neighbouring molecules ~10^7
times/s and can diffuse several mm/s at 37degrees
oThis gives them a viscosity similar to olive oil (100x that of water) means that
membranes act like fluids
Uncatalysed lateral diffusion
FRAP experiments show lateral diffusion
Fluorescence recovery after photobleaching: shows that lipids can easily move laterally in a
lipid bilayer label the lipids with dye then laser bleach it
Uncatalysed trans-bilayer ("flip-flop") diffusion very very slow and rare
Phase transitions in phospholipid bilayers
Heat disorders the interactions between the fatty acid tails to change the membrane from a
gel to a fluid state (oil on a pan)
Lipids determine membrane properties
A cell has many types of membrane, each with different properties due to their protein and
lipid composition cell controls what is going on
We have already seen the effects of different fatty acids on membrane fluidity
oLong chain fatty acids aggregate extensively to give low fluidity (gel-like state)
saturated… lot of opportunity for hydrophobic effect of tail
oShort chain fatty acids have less surface area to aggregate and increase fluidity
oUnsaturated fatty acids also aggregate less extensively and increase fluidity
Composition determines thickness cholesterol increases thickness by ordering fatty acid tails, and
stabilises head group interactions visual representation of membrane properties for lipids… SM is
more rigid.. Cholesterol doesn't do much
Composition and curvature
Curvature is determined by the relative side of the head group to the size of fatty acid tails
oPC: large head group, large tails, cylinder-shaped, flat membrane
oPE: small head group, large tails, cone-shaped membrane
Some aspects of membrane function require curvature they take advantage of curvature
Viral budding
Formation of vesicles e.g. At the plasma membrane
Stability of curved structure e.g. Microvilli in the small intestine
Proteins also help to stabilise curved membranes
Leaflets differ in composition
Membranes have an asymmetric distribution of lipids in the leaflets of their membranes
For example: human red cells
oExoplasmic leaflet - rich in sphingolipids + PC (less fluid)
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oCytosolic leaflet - rich in PE/PS/PI (more fluid)
Cholesterol is relatively evenly distributed in both leaflets
Asymmetric distribution of phospholipids between the inner and outer leaflets of red blood cell
plasma membrane gives you an idea of which phospholipids have what leaflet bias
Two faced nature of bilayers
Two-faces can be defined
oCytosolic faces cytosol
oExoplasmic extracellular, outer environment
How do we know this? Take advantage of discoveries some people have already made
We can use enzymes called phospholipases to determine which PLs are on the outside of
membranes
These enzymes cannot cross the membrane and so only remove head-groups exposed on
one face of the membrane
How does asymmetry arise?
Lipids do not spontaneously flip from one leaflet to the other no unassisted flipping
Specific enzymes can catalyse translocations flipping, deposit them in particular leaflets etc.
((((youre just meant to understand concept not memorise))))
Sphingomyelin is synthesised in the exoplasmic face of the golgi which becomes the
exoplasmic face of the plasma membrane
Glycerophospholipids are synthesised on the cytosolic face of the ER which becomes the
cytosolic face of the ER which becomes the cytosolic face of the plasma membrane contrary to
other ones
PC arrives at the plasma membrane on the cytosolic side but is transported to the other
leaflet by "flippase" enzymes which require energy from ATP hydrolysis enriched on the other
side of the membrane
Catalysed transbilayer translocations
Flippase: (P-type ATPase) moved PE and PS from outer to cytosolic leaflet one direction… cytosolic
side
Floppase: (ABC transporter) moved phospholipids from cytosolic to outer leaflet other direction
Scramblase: moves lipids in either direction, toward equilibrium
Membrane mircrodomains
Microdomains control lateral diffusion
Example: stable associations of sphingolipids and cholesterol: lipid rafts some chemicals are
more strongly bonded than others and stick together making lipid rafts
o can be disrupted by methyl-3-b-cyclodextrin (removes cholesterol from
membranes) or the antibiotic filipin (sequesters cholesterol)
oSpecific signalling proteins associated with lipid rafts
Membrane proteins any protein located at the membrane (through and attached)
Membrane proteins are located in or on the membrane bilayer
Different membranes have different composition in terms of lipid:protein ratio
some membranes more protein than lipid
oBacterial, mitochondrial, chloroplast
More than one third of genes code for membrane proteins
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Document Summary

Lipid mobility in phospholipid bilayers how they can move. Lipids have two main types of motion: o o. Spinning without changing location not interesting or important. Lateral diffusion - movement with the same leaflet rapid. Phospholipids exchange position with neighbouring molecules ~10^7 times/s and can diffuse several mm/s at 37degrees o. This gives them a viscosity similar to olive oil (100x that of water) means that membranes act like fluids. Fluorescence recovery after photobleaching: shows that lipids can easily move laterally in a lipid bilayer label the lipids with dye then laser bleach it. Uncatalysed trans-bilayer (flip-flop) diffusion very very slow and rare. Heat disorders the interactions between the fatty acid tails to change the membrane from a gel to a fluid state (oil on a pan) A cell has many types of membrane, each with different properties due to their protein and lipid composition cell controls what is going on.

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