Membrane Structure Flashcards
Fluid Mosaic Model
- fluid phospholipid bilayer with proteins embedded
Evidence:
-Lipid bilayer, biochemical and EM evidence from RBC plasma membranes
-Mosaic, freeze fracture
Membrane Composition
-Lipid - bilayer
Protein - peripheral and integral
Carbohydrate - linked to lipid or protein
- proportion of lipid and protein depends on function of membrane
Composition: Lipids and Protein
Myelin sheath - 82% lipid, 18% protein
Mitochondrial inner membrane - 24% lipid, 76% protein
Lipid Composition
- three membrane lipid types ( phospholipids, cholesterol, glycolipids)
- amphipathic
Glycolipids composition
- carbohydrate
- neutral glycolipids - cerebrosides and globosides
- one or more uncharged sugar residues
- blood group determinants (ABO system)
- Carbohydrate:
- Gangliosides: complex oligosaccharides, one or more sialic acid residues ( has net (-) charge), errors in metabolism cause lysosomal storage diseases such as Tay-Sachs and Gaucherie where Gangliosides accumulate in the brain
- pattern of sugar residues is variable
- always in outer leaflet of cell membrane and inner leaflet of organelles, contribute to glycocalyx
Glycocalyx
- fuzzy coat on external surface
- carbohydrate residues on glycolipids and glycoproteins
- protects GI membranes from digestion
Peripheral Proteins
- non-covalent bonds with protein or lipids (H bonds, or ionic interaction)
- Removed by high salt or extreme pH
Integral Membrane proteins
- embedded in lipid bilayer
- removed by detergent
- Three types: single leaflet, single pass transmembrane, multiple pass transmembrane
Single Leaflet Integral proteins
- lipid is covalently bound to single AA
- Outer leaflet: GPI anchor
- Inner leaflet:
- Fatty acid: Myristic acid is added to N-terminal Gly, Palmitic acid added to internal Cys
- Long Chain hydrocarbons: prenyl group is aged to a C-terminal Cys, Farnesyl-Lamins, Geranylgeranyl - small moneomeric GTPases
Alpha-helical transmembrane Proteins
- transmembrane domain: single pass and multipass
- Extracellular (glycosylated) and cytoplasmic domains
Single Pass Transmembrane Proteins
- hydrophobic alpha-helix in membrane
- polar domains on both sides of membrane
Multipass Transmembrane Proteins
- alternating stretches of hydrophobic and hydrophilic AA
- hydrophobic regions form the multiple transmembrane domains
- hydrophilic regions form the polar intracellular and extracellular domains
- can make aqueous channels in membranes
- side chains are arranged so that hydrophobic ones contact lipid, hydrophilic ones surround the central opening
Membrane Properties
- asymmetry
- fluidity
- specialized domains
Asymmetry
- distribution of lipids not the same in both halves of the bilayer
- proteins have specific orientation (extracellular and cytoplasmic domains)
- Glycocalyx - carbohydrate on outside
External leaflet has more
- phosphatidylcholine, sphingomyelin, glycolipids
Internal leaflet has more
Phosphatidylserine, phophatidylethanolamine, phosphatidylinositol
Asymmetric Orientation of Transmembrane proteins
-orientation of proteins, functional portions of proteins are oriented on either the extracellular or cytoplasmic side of the membrane
Receptors - ligand binding domain will be on outside of membrane, effector portion will be on the cytoplasmic side of the membrane where it can transmit a signal to the cell
Motion of lipids in membranes
- rotate in place
- hydrophobic tails flex
- flip flop across membrane (phospholipids rare, cholesterol common)
- lateral movement
Fluidity
- movement of lipids in the membrane
- Depends on: temp, lipid composition
- lipid disordered = more fluid
- Lipid ordered = less fluid
Affect of Lipid Composition on Fluidity
- shorter fatty acid chains make membrane more fluid
- unsaturated phospholipids with bend in tail make membranes more fluid
- cholesterol with rigid steroid rings - decrease fluidity at high temp, increase fluidity at low temp to prevent freezing
Protein Mobility
- proteins can move within membrane (rotate, lateral diffraction)
- experimental evidence for mobility of membrane proteins (cell fusion)
Cell Fusion Experiment
- Antibodies to human and mouse membrane proteins tagged with fluorescent dyes
- cells fused and antibodies added
- initially proteins separate
- diffuse evenly over time
Membrane Domains
1) epithelial cell
2) Domains:
- apical - faces lumen or external surface
- basolateral - faces internal side of tissues and adjacent cells
3) maintained by tight junctions
4) restricts proteins to specific regions
- important functional implications
5) some proteins are restricted to specific membrane domains
6) location serves function
Lipid Rafts
Microdomains that are enriched in: sphingolipids containing saturated, long chain fatty acids, cholesterol, GPI-linked and acyl acted proteins
1) Regional differences in fluidity
- composition makes rafts less fluid
- restrict movement of proteins
2) important for signal transduction
- receptor dimerization
- association with effector molecules
