M7 Van- Containment: from lipids to membranes

what are the three main types of membrane lipids?

• phosphoglycerides (‘typical’ phospholipid)- glycerol linker, phosphate group + two fatty acids, all joined by ester bonds

• sphingolipids (another phospholipid)- sphingosine linker, phosphate group, joined by an ester bond, + two fatty acids, joined by amide bonds

• hopanoids + cholesterol- flat, hydrophobic molecules with saturated rings that intercalate into the bilayer and increase membrane stiffness

  • hopanoids are pentacyclic compounds, found in prokaryotic membranes

  • cholesterol is a tetracyclic compound, found in eukaryotic membranes

how can phospholipids vary?

variation in the tails:

• tail length (longer = less fluid)

• fatty acid saturation, normally only in one tail- cis double bonds are common, trans are rare (unsaturated = less tightly packed + more fluid)

variation in the heads:

• head groups attached to the phosphate are involved in protein interactions, signalling and recognition

• eg. glycerol, serine, glucose, choline, ethanolamine, inositol

compare diffusion of lipids within and between membrane leaflets

• diffusion within leaflets is very fast

• diffusion between leaflets is rare, because it is difficult to get the hydrophilic head group past the hydrophobic tails, but can be catalysed by flippases

  • this causes asymmetry in the membrane, because there will be more phospholipids in one leaflet than the other

what are the three types of membrane protein?

• integral membrane proteins have transmembrane domains (alpha helices, helical bundles and beta barrels) which have many hydrophobic residues that interact with the fatty acids

• peripheral membrane proteins associate with membrane lipids and proteins via polar interactions, so they can be dirsputed by high salt concentrations

• membrane-anchored proteins have lipid tails that are added post-translationally to interact with the fatty acids

in what three ways are membrane-anchored cytoplasmic proteins lipidated?

• S-acylation- post-translational, reversible modification on cysteine residue by a thioester bond

• N-myristoylation- post-translational or co-translational (during translation), irreversible modification of an N-terminal glycine residue (once methionine removed) by an amide bond

• prenylation- post-translational, irreversible modification of cysteine residue near the C-terminus by a thioether bond

in what two ways are membrane-anchored extracellular proteins lipidated?

in prokaryotes:

• lipoprotein- post-translational modification on N-terminal cysteine after a signal peptide has been removed

in eukaryotes:

• GPI anchor- co-translational modification at C-terminus

how and why are membranes asymmetrical?

• different lipids aren’t evenly distributed between leaflets due to flippase action

• proteins are asymmetrical and can’t flip

• different PTMs are found on the cytoplasmic and extracellular sides of proteins (eg. outer environment is more oxidative, so disulphide bridges mostly form outside the cell)

what are lipid nanodomains?

• lipid nanodomains/rafts are localised membrane regions with distinct lipid compositions that can attract different proteins

• these robust regions arrange membrane proteins into functional clusters, and alter local membrane rigidity

what are the different sources of energy for active transport membrane proteins?

• light

• ATP from metabolism

• the electrochemical gradient of another molecule- coupled transport

  • symporters/cotransporters move the two molecules in the same direction

  • antiporters/exchangers move the two molecules in opposite directions across the membrane

how are proteins secreted co-translationally?

• proteins to be secreted contain a signal peptide sequence at the N-terminus

• as the ribosome translates the protein, once the signal peptide emerges, a signal recognition particle (SRP) will bind, which pauses translation

• the SRP binds to an SRP receptor on a membrane, so that the signal peptide can go through a translocator across the membrane

• SRP dissociates so translation can continue

• the signal peptidase enzyme cleaves the signal peptide off at the end

  • in prokaryotes, the membrane is the plasma membrane, so the protein is excreted straight out the cell

  • in eukaryotes, the membrane is the rough ER, so the proteins must go through the secretory pathway for excretion via vesicles

how are membrane proteins integrated co-translationally?

• integral membrane proteins contain a signal peptide sequence at the N-terminus

• as the ribosome translates the protein, once the signal peptide emerges, a signal recognition particle (SRP) will bind, which pauses translation

• the SRP binds to an SRP receptor on the plasma membrane, so that the signal peptide can begin to go through a translocator across the membrane

• SRP dissociates so translation can continue

• when hydrophobic alpha helices are translated, these will get recognised as a transmembrane domain

• the signal peptidase enzyme cleaves the signal peptide off at the end