MODULE 2: biomembranes Flashcards
effects of chain length and double bonds on phospholipids
increase chain length = increase stability = increase melting point
increase chain length = increase hydrophobic character = decrease solubility
increase no. double bonds = not tightly packed = decrease melting point
trans bonds = tighter
cis bonds = looser (common)
sphingolipids
major membrane component
derivatives of amino acid sphingosine
n-acyl fatty-acyl derivatives of sphingosine called ceramides
lipid aggregates
lipids can form structures other than lipid bilayer
micelle:
- lyphosome or vesicle
- individual units are wedge shaped
vesicle:
- bilayer with aqueous compartment in centre
stabilisation of bilayers
ionic bonds between head groupd and hydrogen bonds with water
van der waals interactions between fatty acid tails
lipid mobility in bilayers
FRAP experiments
- spinning:
- spin without changing location
- rotation around long axis - lateral diffusion:
- movement with same leaflet
- phospholipids exchange position with neighbouring molecules ~ 10^7 times/second
- can diffuse several mm/s at 37ºC
- this gives viscosity similar to olive oil
FRAP experiments show lateral diffusion
FRAP = fluorescent recovery after photobleaching
- label lipid with fluorescent dye
- use laser to bleach part of surface
- non-bleached lipids move into bleached area (recovery)
uncatalysed transbilayer (“flip flop”) diffusion very slow. hydrophilic head dragged through hydrophobic environment (t1/2 in days)
gel/fluid transitions in phospholipid
heat disorders the interactions between fatty acid tails to change membrane from gel to fluid state
lipids determine membrane properties
long chain fatty acids = gel
short chain fatty acids = fluid
unsaturated fatty acids = fluid
sphingomyelin (SM) associates into a thicker, more gel-like bilayer than phospholipids
cholesterol increases thickness by ordering fatty acid tails and stabilises head group interactions
curvature of phospholipids
PC = cylinder shape = flat membrane
PE = cone shape = curved membrane
functions that require curvature:
- viral budding
- formation of vesicles
- stability of curved structures
proteins help stabilise curved membranes
asymmetry in leaflet composition
how does asymmetry arise?
most membranes have asymmetric distribution of lipids in leaflets of membrane
e. g. human blood cells
- exoplasmic leaflet is rich in shpingolipids, PC and is less fluid
- cytosolic leaflet is rich in PC, PE and PI and is more fluid
- cholesterol evenly distributed
specific enzymes catalyse translocations, it is not spontaneous
sphingomyelin is synthesised in exoplasmic face of Golgi which becomes exoplasmic face of plasma membrane
glycerophospholipids are synthesised on cytosolic face of ER which becomes cytosolic face of plasma membrane
PC arrives at plasma membrane on cytosolic side but is transported to other leaflet by “flippase” enzymes. energetically unfavourable as it requires energy from ATP hyrolysis
flippase = outside to inside floppase = inside to outside scramblase = towards equilibrium
membrane proteins
types of membrane proteins
structure of membrane protein
functions:
- transport
- receptors
- adhesion molecules
- lipid synthesis
- energy transduction
- more
integral:
- firmly associates with membrane
- span membrane
- membrane spanning domain = hydrophobic
- extramembrous domain = hydrophilic
- released by detergent
lipid anchored:
- protein covalently linked to more than 1 lipid
- lipid embedded in leaflet
- protein doesn’t enter bilayer
- released by phospholipase C
peripheral:
- adhere only temporarily to membrane
- released with milder treatment
- no contact with hydrophobic core
- forms hydrophilic interactions with membrane surface
soluble proteins have many different folds
integral membrane proteins can be:
- transmembrane alpha-helices (common)
- transmembrane beta-sheets
alpha-helix proteins
alpha-helix = 20-25 amino acids, perpendicular to bilayer
alpha-helical domains embed in hydrophobic core, therefore there are interactions between hydrophobic aa side chain and fatty acid tails, and ionic interactions with head group
hydrophobic aa chains face outward. peptide bonds face inward to give H+ bonding
beta-barrel proteins
beta barrel = 12, 16, 18, 22 strands, antiparallel to bilayer
hydrophobic outside inserts to membrane
hydrophobic insides of barrel create aqueous pore
lipid anchoring of proteins
water-soluble proteins can be attached to membranes by covalently linking to:
- fatty acids via N-termius i.e. acylation (e.g. myristate = C14 and palmitate = C16)
- prenyls via 2 modifications at a Cys residues at or near C- terminus i.e. prenylation
- GPI via phosphoethanolamine and variable sugars via C-terminus
p-type ATPases
- cation transporters
- 70 in human genome
- phosphorylates on Asp as part of cycle
- 8-10 TM helices
e. g. Ca ATPase
- SERCA pump
- uniporter for Ca2+
e. g. Na+ K+ ATPase
- antiporter 3Na+/2K+
- create Vm = 50-70mV
- causes membrane potential
- 25% energy in human used in this reaction
f and v type ATPases
proton transport driven by ATP hydrolysis:
- F0 (TM) component: after inhibition by oliomycin
- F1 component: 1st factor isolated
- F1 rotates to open and close channel
V-type structually related (V0, V1).
- acidifies intracellular compartments
transporters change pH (movement of p+)
ABC transporters
ABC = atp binding cassette
pump aa’s, peptides, proteins, metal ions, lipid compounds (drugs)
MDR1: multi-drug transporter
- resistance of tumours to drugs
CFTR: Cl- channel
- defective transport makes mucus thick: bacteria grow
- indirectly causes cystic fibrosis
