Membrane Structure

Question 1

Fluid Mosaic Model

Answer 1

• fluid phospholipid bilayer with proteins embedded
  Evidence:
  -Lipid bilayer, biochemical and EM evidence from RBC plasma membranes
  -Mosaic, freeze fracture

Question 2

Membrane Composition

Answer 2

-Lipid - bilayer
Protein - peripheral and integral
Carbohydrate - linked to lipid or protein
- proportion of lipid and protein depends on function of membrane

Question 3

Composition: Lipids and Protein

Answer 3

Myelin sheath - 82% lipid, 18% protein

Mitochondrial inner membrane - 24% lipid, 76% protein

Question 4

Lipid Composition

Answer 4

• three membrane lipid types ( phospholipids, cholesterol, glycolipids)
• amphipathic

Question 5

Glycolipids composition

Answer 5

• 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

Question 6

Glycocalyx

Answer 6

• fuzzy coat on external surface
• carbohydrate residues on glycolipids and glycoproteins
• protects GI membranes from digestion

Question 7

Peripheral Proteins

Answer 7

• non-covalent bonds with protein or lipids (H bonds, or ionic interaction)
• Removed by high salt or extreme pH

Question 8

Integral Membrane proteins

Answer 8

• embedded in lipid bilayer
• removed by detergent
• Three types: single leaflet, single pass transmembrane, multiple pass transmembrane

Question 9

Single Leaflet Integral proteins

Answer 9

• 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

Question 10

Alpha-helical transmembrane Proteins

Answer 10

• transmembrane domain: single pass and multipass

- Extracellular (glycosylated) and cytoplasmic domains

Question 11

Single Pass Transmembrane Proteins

Answer 11

• hydrophobic alpha-helix in membrane

- polar domains on both sides of membrane

Question 12

Multipass Transmembrane Proteins

Answer 12

• 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

Question 13

Membrane Properties

Answer 13

• asymmetry
• fluidity
• specialized domains

Question 14

Asymmetry

Answer 14

• distribution of lipids not the same in both halves of the bilayer
• proteins have specific orientation (extracellular and cytoplasmic domains)
• Glycocalyx - carbohydrate on outside

Question 15

External leaflet has more

Answer 15

• phosphatidylcholine, sphingomyelin, glycolipids

Question 16

Internal leaflet has more

Answer 16

Phosphatidylserine, phophatidylethanolamine, phosphatidylinositol

Question 17

Asymmetric Orientation of Transmembrane proteins

Answer 17

-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

Question 18

Motion of lipids in membranes

Answer 18

• rotate in place
• hydrophobic tails flex
• flip flop across membrane (phospholipids rare, cholesterol common)
• lateral movement

Question 19

Fluidity

Answer 19

• movement of lipids in the membrane
• Depends on: temp, lipid composition
• lipid disordered = more fluid
• Lipid ordered = less fluid

Question 20

Affect of Lipid Composition on Fluidity

Answer 20

• 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

Question 21

Protein Mobility

Answer 21

• proteins can move within membrane (rotate, lateral diffraction)
• experimental evidence for mobility of membrane proteins (cell fusion)

Question 22

Cell Fusion Experiment

Answer 22

• Antibodies to human and mouse membrane proteins tagged with fluorescent dyes
• cells fused and antibodies added
• initially proteins separate
• diffuse evenly over time

Question 23

Membrane Domains

Answer 23

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

Question 24

Lipid Rafts

Answer 24

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