BC368Biochemistry of the Cell II

BC368Biochemistry of the Cell II

Biological Membranes Chapter 11: Part 1February 10, 2015

“Possibly the decisive step [in the origin of life] was the formation of the first cell, in which chain molecules were enclosed by a semi-permeable membrane which kept them together but let their food in.” J. B. S. Haldane,

1954

Plasma MembranePlasma Membrane

Plasma MembranePlasma Membrane

Membrane is composed of:

A. Lipids Phospholipids Sterols

B. Proteins Integral Peripheral

C. Carbohydrates Glycolipids Glycoproteins

Plasma MembranePlasma Membrane

Plasma MembranePlasma Membrane

Variable components in different membrane types

Membrane LipidsMembrane Lipids

Amphiphilic lipids

Major types: phospholipids, glycolipids, sterols

Glycolipid

sphingosine

glycerophospholipid sphingophospholipid

PhospholipidsPhospholipids

Two classes: glycerophospholipids (aka phosphoglycerides) and sphingophospholipids Fig 10-7

PhospholipidsPhospholipids

Two classes: glycerophospholipids (aka phosphoglycerides) and sphingophospholipids

Two fatty acids; phosphate and polar “head group” on glycerol.

Vary in the FA’s and head group.

Membrane Lipids: 1A. GlycerophospholipidsMembrane Lipids: 1A. Glycerophospholipids

Membrane Lipids: 1B. SphingophospholipidsMembrane Lipids: 1B. Sphingophospholipids

Named for the enigmatic Sphinx

Common in nerve and brain cell membranes

Membrane Lipids: 1B. SphingophospholipidsMembrane Lipids: 1B. Sphingophospholipids

Named for the enigmatic Sphinx

note amidelinkage

Sphingosine replaces glycerol, so only 1 FA tail

Example: sphingomyelin

Membrane Lipids: 1B. SphingophospholipidsMembrane Lipids: 1B. Sphingophospholipids

Head group = phosphocholine or phosphoethanolamine

GlycolipidsGlycolipids

Two classes: glycosphingolipids and galactolipids

Fig 10-7

Membrane Lipids: 2A. GlycosphingolipidsMembrane Lipids: 2A. Glycosphingolipids

Sphingolipids with carbohydrate head group; common on cell surfaces

Examples: cerebrosides and gangliosides

Glucose or galactose

SugarSugar

Ganglioside

Membrane Lipids: 2B. GalactolipidsMembrane Lipids: 2B. Galactolipids

Diglycerides with galatose groups

Common in plant (thylakoid) membranes

Membrane Lipids: 3. SterolsMembrane Lipids: 3. Sterols

Cholesterol and cholesterol-like compounds

Lipid Components of MembranesLipid Components of Membranes

Lipid composition varies across different membranes.

Fig 11-2

Lipid composition varies across the two leaflets of the same membrane.

Lipid Components of MembranesLipid Components of Membranes

Turnover of Membrane LipidsTurnover of Membrane Lipids

Fig 10-16

Defects in Membrane TurnoverDefects in Membrane Turnover

Deposits of gangliosides in Tay Sachs brain

Lipids spontaneously aggregate in water as a result of the Hydrophobic Effect.

Lipid AggregatesLipid Aggregates

Amphiphilic lipids form structures that solvate their head groups and keep their hydrophobic tails away from water.

Above the critical micelle concentration, single-tailed lipids form micelles.

Lipid AggregatesLipid Aggregates

Fig 11-4

Double-tailed lipids form bilayers, the basis of cell membranes.

Lipid AggregatesLipid Aggregates

Bilayers can form vesicles enclosing an aqueous cavity (liposomes). Fig 11-4

Fig 11-4

Membrane ProteinsMembrane Proteins

Integral proteins (includes lipid-linked): need detergents to remove

Peripheral proteins: removed by salt, pH changes

Amphitropic proteins: sometimes attached, sometimes not

Usually alpha-helical, ~20-25 residues, mostly nonpolar.

Example: glycophorin of the erythrocyte.

Single Transmembrane Segment ProteinsSingle Transmembrane Segment Proteins

Fig 11-8

7 alpha-helix motif is very common.

Example: bacteriorhodopsin

Multiple Transmembrane Segment ProteinsMultiple Transmembrane Segment Proteins

Fig 11-10

Multiple transmembrane segments form β sheets that line a cylinder.

Example: porins.

Beta Barrel Transmembrane ProteinsBeta Barrel Transmembrane Proteins

Fig. 11-14

Attached lipid provides a hydrophobic anchor.

Lipid-Linked Membrane ProteinsLipid-Linked Membrane Proteins

An important lipid anchor is GPI (glycosylated phosphatidylinositol.

On exoplasmic face only

Membrane CarbohydratesMembrane Carbohydrates

An example is the blood group antigens

On exoplasmic face only

Membrane CarbohydratesMembrane Carbohydrates

glycosphingolipids

At its transition temperature (TM), the bilayer goes from an ordered crystalline state to an a disordered fluid one.

Membrane DynamicsMembrane Dynamics

Fig 11-16

Phospholipids in a bilayer have free lateral diffusion.

Membrane DynamicsMembrane Dynamics

Fig 11-17

Phospholipids in a bilayer have restricted movement between the two faces.

Membrane DynamicsMembrane Dynamics

Fig 11-17

Flippases, floppases, and scramblases catalyze movement between the two faces.

Membrane DynamicsMembrane Dynamics

Fluid Mosaic

Fluorescent Recovery After PhotobleachingFluorescent Recovery After Photobleaching

Fluorescent tag is attached to a membrane component (lipid, protein, or carbohydrate).

Fluorescence is bleached with a laser.

Recovery is monitored over time.

Fluorescent Recovery After PhotobleachingFluorescent Recovery After Photobleaching

FRAP Movie

Fig. 11-20

Some membrane proteins have restricted movement.

May be anchored to internal structures (e.g., glycophorin is tethered to spectrin).

Protein Mobility in the MembraneProtein Mobility in the Membrane

Fig. 11-21

Lipid rafts are membrane microdomains enriched in sphingolipids, cholesterol, and certain lipid-linked proteins.

Thicker and less fluid than neighboring domains.

Protein Mobility in the MembraneProtein Mobility in the Membrane

Lipid rafts are membrane microdomains enriched in sphingolipids, cholesterol, and certain lipid-linked proteins.

Thicker and less fluid than neighboring domains.

Protein Mobility in the MembraneProtein Mobility in the Membrane

Lipid Rafts

Nature Reviews Molecular Cell Biology 4, 414-418 (May 2003)

Nature Reviews Molecular Cell Biology 4, 414-418 (May 2003)

Domains of gel/fluid lipid segregation in a model membrane vesicle, which is a mixture of fluid dilaurylphosphatidylcholine phospholipids with short, disordered chains and gel dipalmitoylphosphatidylcholine phospholipids with long, ordered chains. A red fluorescent lipid analogue (DiIC18) partitions into the more ordered lipids, whereas a green fluorescent lipid analogue (BODIY PC) partitions into domains of more fluid lipids. These domains in a model membrane are much larger than the domains of cell membranes.