The Plasma Membrane Flashcards
what are the role of compartments?
- to get signals to meet
- recruit signals with proteins in the membrane so the signalling molecules are ready next to each other
- designate certain compartments for specific signalling pathways
how do lipids assemble?
spontaneously assembly
what are most lipids?
phospholipids
what is a micelle?
- head groups are out
- tails are pointing inwards
- shape of a globe
- not generally formed in biological systems
what is a bilayer?
- heads outside and inside (they are hydrophilic)
- tails are inside the layer (hydrophobic)
- can form a liposome and form a flat bilayer
- the shape of lipids can determine whether it becomes a flat bilayer or a round structure
what happens if the lipid is shaped like a cone?
- the head has a much larger surafce area than the tail
- lipids will form a circle (shape of a micelle)
- same applies in a bilayer forms a liposome
what happens if the lipid is shaped like a cylinder?
- same cross section as the tail
- forms a bilayer
why does the lipid bilayer need to close up?
cant be exposed to water at the edges
what is membrane curvature determined by?
shape of lipid
what lipid shapes do vesicles contain?
lipids that slightly cone shaped so they curve
is the membrane gel or fluid like?
- gel-fluid transition of membranes is temperature dependent
- transition temperature depends on membrane composition
- organisms living at different temperatures need to control their membrane composition to maintain the correct fluidity
what is the fluid mosaic model?
- things can move around but still keeps a barrier
how can you visualize a membrane with rabbit erythrocytes in an electron micrograph?
- membranes stained with ricin
- ricin binds to sugars on the surface of the plasma membrnae
- doesn’t bind to inside components
- can see both sides of the membrane
- inside and outside are very different
- proves that the membrane is asymmetrical
what does photobleaching show of a membrane?
- fluorescence recovery after photo bleaching (FRAP) of a membrane bound dye
- clustering of membrane components
- shows free diffusion in the membrane
- not every membrane component domain diffuse through
how is thickness determined?
- by phospholipids
- saturated acyl chains (non-fluid)
- unsaturated (fluid)
what do steroids effect?
- they increase lipid packing and thickness
why is membrane thickness important?
- membrane proteins choose which membrane they go to based on thickness
what does fine tuning curvature, fluidity and thickness allow control over?
- lipid and protein diffusion
- membrane plasticity
- protein conformational change for functions (transport, signalling and enzyme activity)
where are lipids initially made?
in the smooth ER
- modulates kind of phospholipid membrane composition and therefore tightly control how you make phospholipids
how are phospholipids made?
- acyl transferase and phosphatase genes are the basic phospholipid building block of DAG
- phospholipids are synthesised separately
- different acyl transfereases can output different fatty acid chains
- large diversity (many possible acyl chain and head group combinations)
what are the roles of transferases?
they can stick on head groups (this can be modified)
how is there lipid remodelling in the secretory pathway?
- unsaturated fatty acid chains replaced with more saturated (ER to PM)
- more cholesterol and spingolipids in late secretory pathway
- carbohydrate head groups of glycolipids to glycans in the Gollgi
- membrane becomes more asymmetrical and thick towards the plasma membrane
what is vesicle lipid trafficking?
- some phospholipids packaged in vesicles in the ER
- changes membrane composition
what is free diffusion?
- some arent as hydrophobic and so can move
what is an LTP?
- lipid transfer protein
- can grab phospholipids from one membrane and move them to another
what are membrane contact sites?
- allowed lipid transfer much more fficiently (important in maintaining composition)
- membranes are close so LTP can sit between them and move back and forth
- exist between compartments that may not necessarily otherwise communicate
what are the functions of MSC?
- lipid transfer
- coordinated Ca2+ release facilitate signalling and cytoskeletal dynamics
- aid in organelle fission
- generate a new membrane structure
- aid in protein sorting between organelles
what is cholesterol?
- essential component in membranes in humans
- alters membrane fluidity
- part of ‘membrane rafts’
- has this effect because of its structure
what is the structure of cholesterol?
- a small head group which is hydroxyl, the rest of it is hydrophobic
- hydrophobic part is very rigid
- a ring structure
- wedges itself into the membrane and stops the membrane moving around
how is cholesterol made and transported?
- not made by host human cells
- transported to all tissues by LDL
- binds to LDL receptor
- delivers cholesterol into the cell through endocytosis
- if theres too much then the LDL receptor isnt made
- LDL just sits in the body waiting to be used, it will sit and deposit in the arteries (clogging)
what is HDL?
transport cholesterol from the cells to the liver to be degraded
where are glycolipids made?
made in the ER and Golgi by the addition of monosaccharides
how are glycolipids made?
- addition of monosaccharides including ceramide
- first addition are on the cytosolic or luminal faces of the Golgi and ER
what additions happen in the Golgi?
most additions, often branched oligosaccharides
where are glycolipids important?
- important function of lipid rafts
- important in immunity (blood groups)
- gangliosides (components of neuronal membranes)
why are membrane proteins important?
- synaptic vesicle is full of proteins
- lipid bilayer, lipids and lots of protein
- proteins alter the structure and function of membranes too
what can membranes be covered in?
glycoproteins and glycolipids
what are peripheral membrane proteins?
- proteins attached to the surface
- or lipid binding
- they bind the membrane surface and do not cross the membrane
- head group of phospholipid can bind to a groove in the protein (polar pocket)
- or a groove that recognises a specific ligand
- hydrophobic protrusion that penetrates into the membrane
- clusters of basic residues that bind anionic phospholipid head groups
what are the clusters of basic residues that bind anionic phospholipid head groups?
- BAR domain has a positive charged domain
- has 2 effects: can shape the membrane sometimes and attach
how can amphipathic helices cause membrane deformation?
- one side hydrophilic and one side hydrophobic
- polar and hydrophobic amino acids on the opposite sides of the helix
- sits in the outer leaflet
- wedges membrane and initiates curvature
how can loop insertion cause membrane deformation?
- inserts deeper
- loops hydrophobic amino acids
how can curved lattices cause membrane deformation?
- lattices bind cargo proteins but the lattice forms a curved polymer
how can BAR domain proteins cause membrane deformation?
- proteins bind the bilayer via a curved surface eg BAR domain containing proteins
what is the association of peripheral proteins with membranes described as?
dynamic - goes on and off the membrane
what does the association of peripheral protein with membranes depend upon?
- type of membrane
- Ca2+ concentration
- availability of lipid species
- shape of membrane
how are peripheral proteins anchored in the membrane?
- have a lipid anchor, a lipid tail is added to the protein which inserts into the membrane
- lipid anchors can be tucked away when the protein is in the cytosol
is lipidation reversible?
yes
what is a GPI anchor?
essentially a phospholipid and then a glycan
- associated with lipid rafts
- on the outside
what is a transmembrane protein?
- an integral membrane protein
- they cross the membrane so theres proteins on both sides of the membranes
- they are embedded
what is type IV transmembrane protein?
- polytopic (like GPCR)
- cross the membrane several times
- membrane proteins with more than one TM domain
what is type III transmembrane protein?
- crosses the membrane once
- majority is in the cytosol
- tail anchored proteins
- no class signal peptide
- put into the membrane through special machinery
what is type II transmembrane protein?
- carboxyl terminus is the lumen side, NH3+ is in the cytosol
- signal peptide targets it to membrane but stays on cystolic side
what is type I transmembrane protein?
- carboxyl terminus on to cytosol side
- signal peptide guides N terminus across the membrane
what does the alpha helix in the transmembrane protein allow?
- helices allow them to cross the membrane
- the alpha helix spans the membrane
- the helix has a peptide backbone
- carbonyl binds with hydrogen bonds to amino groups
- out from the helix there are side chains
- as long as the amino acids have a hydrophobic side chain you can cross the membrane
how long are the helices that cross the membrane?
helices of around 20 hydrophobic amino acids spans the membrane
what do aromatic amino acids often contact?
lipid head groups
what are non-hydrophobic amino acids in membrane helices?
they have functional roles
- eg positive charges in the voltage sensor of some channels
how can you identify a TM domain?
- look for a stretch of 20 amino acid stretches of hydrophobic amino acids
how long is a transmembrane domain?
matches membrane thickness
what can make membranes more soluble?
detergents
how do detergents effect the membrane?
- a little bit inserts into the bilayer
- more detergent means the membrane breaks up
- a high amount removes lipid into micelles
what components of the membrane can resist solubilzation in some detergents?
lipid rafts
what does decreased membrane fluidity lead to?
- lipid rafts
what are the features of lipid rafts?
- contain a lot of cholesterol
- low fluidity = less diffusion
- have specific interactions (have TM proteins which has cholesterol binding site)
- fatty acid modified lipidated proteins
- GPI anchors prominently found in the rafts
when do lipid rafts occur?
- happens when there is strong association between lipids
- proteins bind lipids via their transmembrane domain or can be lipid anchored to become raft associated
what are the functions of lipid rafts?
- signalling (platform for assembling signalling proteins)
- protein function (rigidity alters protein conformation)
- host pathogen interactions
how is the plasma membrane a barrier?
limiting membrane separates the outside from the inside and therefore needs transport
how do water soluble molecules get through the membrane?
- need proteins to help them through
- water itself needs a protein channel
what do transport proteins do?
- actively transport to increase concentration
why do lipids need to be transported?
they need special transporters to generate lipid asymmetry
how can gradients be generated?
selective membrane transport
what are pumps?
- active transport
- fuelled by energy (ATP)
- high affinity, used to accumulate solutes against large gradients
what are carriers?
- not directly energized
- transporting along a concentration gradient or using a secondary solute
- faster than pumps, slower than channels
what are channels?
- diffusion, pores, passive very fast transport along a concentration gradient regulating open or shut state
- often specific for an ion
- transports water
what is lipid asymmetry?
- need this for the functional working of the lipid bilayer
- synthesis of many phospholipids occurs on the cytoplasmic of the ER
- hence PE and PS are on the correct leaflet but not PC
what are flippases?
transport out to in
what are floppases?
transport in to out
what do flippases and floppases do?
both pumps use ATP to get the phospholipid headgroup across the membrane against its concentration gradient
how is water transported across the membrane?
- aquaporin is a water channel
