General Biochemistry

Chem560 Spring 2016

Lecture 18
Lipid Bilayers and Membrane Proteins
Manal A. Swairjo, Ph.D.
4/7/2016

Chapter 9
Lipid Bilayers

Learning Objectives
Why do glycerophospholipids and sphingolipidsbut not fatty acidsform bilayers?
Explain why lateral diffusion of membrane lipids is faster than transverse diffusion.
What factors influence the fluidity of a bilayer?
Explain the differences between integral and peripheral membrane proteins.
What are the two types of secondary structures that occur in transmembrane
proteins?
Describe the covalent modifications of lipid-linked proteins. Why might some of
these modifications be reversible?

Aggregates of Single-Tailed Lipids

Wedge shaped

Ideal spheroidal micelle

From few hundred molecules

These two are unfavorable due to water-filled center.

Too many lipid monomers per micelle.

Phospholipids (double tailed) form

favorable disk micelles with bilayers

Rectangular shape

Phospholipids in aqueous solution

spontaneously form liposomes

Liposome: spheroid shaped solvent filled

vesicle bound by a single phospholipid
bilayer.
Very stable structures.
Several hundred Angstroms in diameter.
Used for drug delivery because they
readily fuse with cell membranes.

Diffusion in Phospholipid Bilayer

Rare event. Half time of several days.

Reason: polar headgroups have to cross the hydrophobic core.

Occurs all the time. Very fast speed of 1 micron per second.
Therefore, phospholipid bilayers are considered a 2D fluid.
Note this is just a schematic showing the acyl chains as stiff.
In fact they are not.

A more realistic view of the fluid bilayer core

This is a computer generated model.

Molecular dynamics simulation calculations
show that the core is more fluid than the polar
surface.
The acyl chains are in constant motion due to
rotations around the C-C bonds.
Note that the acyl chains interdigitate to form a
tight seal.
Note that water penetrates only in between the
polar head group.
Head groups bob up and down.
Unsaturated acyl chains (with double bonds) kink
and fill the gaps.

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30

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Phase Transition in Lipid Bilayers

Note: why does cholesterol decrease membrane fluidity?

The whole lipid molecule is highly mobile.

The nonpolar tail is wiggling and bending,
hence thin bilayer.
Liquid crystal state.

Nonpolar tails are straight and rigid, hence

thick bilayer.
They form more orderly array.
Gel like solid.

Integral (Intrinsic) Membrane Proteins are Tightly

Membrane Associated

Phospholipid molecules bound to the

protein.
Acyl chains conform to the protein
hydrophobic surface.
The protein thickness matches the
membrane thickness.
Membrane proteins can be extracted from
membranes with detergents (e.g. SDS) and
purified by gel filtration but require
detergent to stay soluble.

Crystal structure of
Aquaporin

Integral Proteins are Asymmetrically Oriented Amphiphiles.

i.e. they are found oriented in one direction relative to the membrane.

Human glycophorin A in
membranes of red blood cells.
Heavily glycosylated and this makes
cell membrane hydrophilic so RBCs
flow easily in blood plasma and do
not stick.

Example of a transmembrane protein: human gylcophorin A.

All transmembrane (TM) segments of membrane

proteins consist of either alpha helices or beta
sheets.

TM segments can be predicted from the

amphiphlicity profiles of the sequence.
Amphipathic helices: their hydrophobic
sides face the membrane core.

Seven Helices: Bacteriorhodopsin

(7-TM protein).

Beta barrel: OmpF porin.

Which face of the beta sheet is hydrophobic?

OmpF porin is a Barrel Trimer and its

Hydrophobic Band Immersed in Membrane

Lipid Modifications Anchor Proteins to Bilayer

Isoprenoids (C15 and C20 shown). They get

enzymatically linked to proteins at a C-terminal
Cys.
Myristoylation: C14 fatty acid attached to N-term
Gly.
Palmitoylation: C16 fatty acid attached to specific
Cys.

Peripheral membrane proteins are on the surface of the bilayer

and dissociate easily. They are double faced. Example: Annexins
bind to bilayer in a calcium dependent manner.

Chapter 9
Lipid Bilayers and Membrane Proteins
Key Concepts
Certain amphiphilic molecules form bilayers.
The bilayer is a fluid structure in which lipids rapidly diffuse
laterally.
Integral membrane proteins contain a transmembrane
structure consisting of helices or a barrel with a
hydrophobic surface.
Lipid-linked proteins have a covalently attached prenyl
group, fatty acyl group, or glycosylphosphatidylinositol
group.
Peripheral membrane proteins interact noncovalently with
proteins or lipids at the membrane surface.