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Flashcards in Membrane Structure Deck (24):
1

Fluid Mosaic Model

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

2

Membrane Composition

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

3

Composition: Lipids and Protein

Myelin sheath - 82% lipid, 18% protein
Mitochondrial inner membrane - 24% lipid, 76% protein

4

Lipid Composition

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

5

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

6

Glycocalyx

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

7

Peripheral Proteins

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

8

Integral Membrane proteins

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

9

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

10

Alpha-helical transmembrane Proteins

-transmembrane domain: single pass and multipass
-Extracellular (glycosylated) and cytoplasmic domains

11

Single Pass Transmembrane Proteins

-hydrophobic alpha-helix in membrane
-polar domains on both sides of membrane

12

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

13

Membrane Properties

-asymmetry
-fluidity
-specialized domains

14

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

15

External leaflet has more

- phosphatidylcholine, sphingomyelin, glycolipids

16

Internal leaflet has more

Phosphatidylserine, phophatidylethanolamine, phosphatidylinositol

17

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

18

Motion of lipids in membranes

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

19

Fluidity

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

20

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

21

Protein Mobility

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

22

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

23

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

24

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