Containment: From Lipids To Membranes Flashcards
Why do we think cell membranes existed before the RNA world?
To prevent diffusion of components
Amphipathic
Having both hydrophilic and hydrophobic parts
What is the hydrophobic effect ?
In water, fatty acids spontaneously form micelles, membranes and vesicles, depending on pH
How large is a micelle?
~20nm
Where are fatty acids produced abiotically
In geysers, catalysed by minerals
What naturally happens to vesicles with content?
- cause osmotic pressure
- tend to grow
- break up: abiotic ‘cell’ division
What do current membranes mainly consist of?
- phospholipids
- hopanoids/steroids
- proteins
Integral proteins aka
Intrinsic proteins
Peripheral proteins aka
Extrinsic proteins
What are the two main classifications of membrane lipids
- Phospholipids
- Hopanoids
What is the main membrane steroid?
Cholesterol
What are the two main classifications of phospholipids?
- phosphoglycérates
- sphingolipids
What structure do phospholipids spontaneously organise themselves into, and why?
- lipid bilayers (membranes)
- they have ‘thicker’ hydrophobic tails
What are the two halves of the phospholipid bilayer referred to as?
Leaflets
What is the hydrophobic effect on phospholipids?
In water, phospholipids spontaneously form lipid bilayers
Describe phosphoglycérides
- 3x components: phosphate, glycerol linker, 2x fatty acids
- polar hydrophilic head
- nonpolar hydrophobic tail
- ester bonds
Give an example of a phosphoglyceride
Phospho-diglyceride
Describe sphingolipids
- 3x components: phosphate, sphingosine linkers, 1x fatty acid
- polar hydrophilic head
- nonpolar hydrophobic tail
- ester bond connects phosphate and sphingosine
- amide bond connects sphingosine and fatty acid
What are factors that can vary in phospholipids?
- tail length (C14-C24)
- tail saturation (C=C v unsaturated)
- head group
Give an example of a sphingolipid
Phospho-ceramide
What do longer fatty acids tails do?
- Increase membrane thickness
- Decrease membrane fluidity
Describe trans fatty acids
- No kink
- rare
Describe cis fatty acids
kink
What does unsaturated lipids do to membrane fluidity ?
Increase it
What are the most common head groups on phospholipids
- Choline
- Ethanolamine
- Glucose
- Glycerol
- Inositol
- Serine
Headgroups have roles in:
- Protein-membrane interactions
- Signalling
- Recognition
In which classification of organisms are hopanoids found?
Prokaryotes
In which classification of organisms is cholesterol found?
Eukaryotes
Describe hopanoids
Pentacyclic compound
Describe cholesterol
- Tetracyclic compound
- steroid
What do hopanoids and cholesterol do?
- intercalate into bilayer
- increase membrane stiffness
Describe hopanoids and cholesterol
Flat, hydrophobic molecules
List the two types of lipid storage
- Lipid droplet
- Triglycerates (fats/oils)
List the 2 types of lipid movement:
- Lateral diffusion
- Transverse diffusion
Describe lateral diffusion of lipids in membranes
- fast
- 1 micrometer per second
Describe transverse diffusion of lipids in membrane
- flip-flop
- rare, depending on lipid
Flippases
Proteins that catalyses flip-flop of specific lipids, causing asymmetry of lipids between leaflets
List the 3 types of membrane protein
1) integral
2) peripheral
3) membrane-anchored
List the 3 types of integral membrane protein
- α-helix
- Helical bundle
- β-bundle
Give an example of an α-helix structure
Receptors
Give examples of helical bundles
- transporters
- enzymes
- receptors
Give an example of a β-barrel
Transporters
Describe integral membrane proteins
Hydrophobic side chains decorate surface of transmembrane regions
TMD
transmembrane domain
Describe peripheral membrane proteins
Proteins that associated with membrane lipids and proteins via polar interactions
List the two types of membrane-anchored proteins
- Cytoplasmic
- Extracellular
Give the 3 main cytoplasmic protein lipidations
- N-myristoylation
- Prenylation
- S-acylation
Describe S-acylation
- PTM
- reversible (not a very strong bond)
- on Cys
- cytoplasmic palmitoyl linked to sulfate on serine residue
Describe N-myristoylation (type of lipidation)
- PTM/ cotranslational
- irreversible, v strong
- on N terminal Gly
- amino group with v strong slide bond on myristoyl attached after N-terminal methionine removal
Describe prenylation
- PTM
- irreversible
- on Cys in C terminal CaaX motif
Give the prokaryotic extracellular protein lipidation
Lipoprotein
Describe lipoprotein lipidation
- PTM
- on N-terminal Cys
Describe the main extracellular eukaryotic protein lipidation
- GPI anchor
- cotranslational
- C-terminal Glycosyl-Phosphatidyl-Inositol
Describe the movement of membrane proteins:
- some move laterally
- no transverse diffusion
Describe membrane asymmetry
- lipid (and protein) distribution over leaflets is not equal
- PTMs are different outside/inside
- maintained by flippases
- conserved during vehicular transport
How are micro/nano domains created in liposomes?
Lipids with different properties
Nanodomain aka
Lipid raft
What is a nanodomain?
- local, robust, dynamic membrane region with physically different lipid and protein composition
Which gases can permeate membranes?
CO2, O2
Which hydrophobic molecules can penetrate membranes?
Benzene, steroids
Which small polar molecules can penetrate membranes?
Water, ethanol (some resistance)
What happens to large, polar molecules on membrane contact
- e.g. glucose, sucrose
- Some get through, most repelled
What happens to charged molecules on membrane contact
- all repelled
- e.g. amino acids, H+, Cl-, Na+, Ca2+
What is passive transport?
Transport in same direction as electrochemical gradient
How can passive transport be achieved?
- Through channels
- Through transporters (inducing conformational change)
- regulated
Describe passive transport
selective for specific molecules
How is passive transport regulated?
- ligand (gated)
- voltage gated
Define active transport
Transport against an electrochemical gradient
Where is the energy for active transport derived from?
- light
- metabolism
- electrochemical gradient of other coupled transported molecules (co-transport)
What are the two types of coupled transport?
- Symporter
- Antiporter
Symporter aka
Cotransporter
Antiporter aka
Exchanger
How does protein translocation occur?
- Hydrophobic SP emerges fro ribosome
- SRP binds to SP; blocks translation
- SRP binds to SRP membrane receptor
- SP enters protein translocator
- SRP and receptor dissociate; translation continues
- Signal peptidase cleaves after SP
- Ribosome dissociâtes post- translation
SP
signal peptide
SRP
- signal recognition particle
- ribonucleoprotein complex
- contains translational pause domain, hinge and SP binding protein
- 4eu5 structure
- very ancient decision and machinery
What is the SRP membrane receptor in eukaryotes?
Plasmamembrane
What is the SRP receptor in eukaryotes
Rough ER
What is the role of the 2nd α-helix in SRP?
- stop signal to translocator
- causes dissociation from translocon
- transmembrane protein stops in the membrane
What is the role of the 3rd α-helix in SRP?
Start signal for translocator
Why is vesicles stage not stable?
It is determined by pH
How are phosphoglycerides created?
Acylation of phosphoglyercol
Describe sphingosine
- apolar long tail
- polar amine and hydroxyls head group
Why are sphingolipids a bit more stable?
Amide bonds
Rigidity synonym
Solidity
Head groups act as
Decorations
Describe the structure of hopanoids and cholesterol
- ring systems
- apolar
- flat surface
- very small hydroxyl polar group
Lateral diffusion is
Very dynamic
Describe flip flopping action
- one leaflet to the other leaflet
- bigger hydrophilic groups are harder to flip
Why flippase?
Creates chemical differences between leaflets
How can integral membrane proteins interact with hydrophobic lipids on the surface?
They are also hydrophobic on the surface
Describe peripheral proteins
- associated with membrane proteins or membrane directly
- contain hydrophilic structures
- have polar interactions
What is a helical bundle?
A hole in the membrane that selectively transports molecules
What is the residue number?
How far along the protein
How do we predict if a protein is hydrophobic?
- regions of hydrophobia through identification of helix number
How to extract peripheral proteins
- high salts and pH
- disturbs polar interactions
X =
Last residue on the protein
Where do lipidation reactions occur?
Cytoplasm
Are lipidations restricted to cell membranes?
No: can occur in mitochondrial and chloroplastic membranes too
GPI anchor function
Tethers extracellular proteins
Are kinases extracellular or intracellular
Intracellular
Describe liposomes
Lots of variation, highly dynamic
What happens under high concentrations of sphingolipids?
- more cholesterol accumulation
- more transmembrane helices
Can zwitterions penetrate cell membranes?
No, they are charged
What does passive mean?
No energy required
What can passive transport be thought of?
Selective diffusion
Protein translocation depends on
The sequence of the protein itself
Why are proteins stuck in the membrane?
Because of the transmembrane domain
