Chapter 10

Membrane Structure

All biological membranes have a common structure each is a very thin

film of lipid and protein molecules held together by noncovalent interactions

The Lipid Bilayer

Membrane lipids are amphipathic molecules, most of which

spontaneously form bilayers

The most abundant membrane lipids are the phospholipids

Phospholipids have a polar head group and

two hydrophobic hydrocarbon tails

The tails are usually fatty acids, and

they can differ in length. One tail
usually has one or more cis-double
bonds, while the other does not.

The shape and amphipathic nature of the

lipid molecules cause them to form bilayers
spontaneouly in aqueous environments.

Hydrophilic and hydrophobic molecules interact differently with water

Packing arrangements of lipid molecules in an aqueous environment

Lipid molecules spontaneously aggregate to bury their hydrophobic tails in the interior
and expose their hydrophilic heads to water. Being cylindrical, phospholipid
molecules spontaneously form bilayers in aqueous environments

The spontaneous closure of a phospholipid bilayer to form a sealed compartment

The formation of a sealed compartment is fundamental to the creation of a living

cell, and this behavior follows directly from the shape and amphipathic nature of
the phospholipid molecule

The lipid bilayer is a two-dimensional fluid

Individual lipid molecules are able to diffuse freely within lipid bilayers.
Demonstrated using synthetic lipid bilayers and
electron spin resonance (ESR) spectroscopy

Liposomes

A black membrane

Phospholipid mobility

The fluidity of a lipid bilayer depends on its composition and its temperature

The membrane becomes more difficult to freeze if the hydrocarbon chains are short
or have double bonds, so that the membrane remains fluid at lower temperatures

The lipid bilayer of many cell membranes is not composed exclusively of

phospholipids, it often also contains cholesterol and glycolipids

Eucaryotic plasma membranes contain large amounts of cholesterol

Four major phospholipids predominate in the plasma membrane of mammalian cells

Lipid bilayers can form domains of different compositions

Lipid phase separation in artificial lipid bilayers

(A) 1:1 mixture of phosphatidylcholine and sphingomyelin
(B) 1:1:1 mixture of phosphatidylcholine, sphingomyelin, and cholesterol

Plasma membrane contains lipid rafts that are enriched in sphingolipids,

cholesterol, and some membrane proteins

Lipid rafts are small specialized areas in membranes where some lipids (primarily
sphingolipids and cholesterol) and proteins are concentrated

Lipid droplets are surrounded by a phospholipid monolayer

The asymmetry of the lipid bilayer is functionally important

The lipid bilayer of human red blood cells

Signaling functions of inositol phospholipids in the cytosolic leaflet of the plasma membrane

Glycolipids are found on the surface of all plasma membranes

Membrane Proteins

Membrane proteins can be associated with the lipid bilayer in various ways

Covalent attachment of a protein to the membrane by a

fatty acid chain or a prenyl group

In most transmembrane proteins the polypeptide chain crosses the lipid bilayer
in an -helical conformation

Membrane regions and preferred amino-acid locations. A snapshot of a lipid bilayer membrane
and its three major regions. Grey, carbon atoms; red, oxygen; white, hydrogen bound to oxygen;
orange, phosphorus. In an a-helix, 20 amino acids (blue) can span the hydrocarbon core, and 10
amino acids (green) can span the interfacial region. Arrows indicate where most of each amino
acid (denoted by its three-letter symbol) would be found at equilibrium based on transfer freeenergy measurements (Nature, 2005, Vol 433, 367-369)

A possible scheme for the membrane-insertion decision, as proposed by Hessa et al. A top
view of the membrane and the translocon pore that crosses it. Inside the pore is a peptide
helix surrounded by water. The pore opens sideways into the membrane, allowing the helix
to interact with the membrane lipids. If the peptide is more compatible with lipid than with
water, it will transfer into the membrane; otherwise, it will continue to be moved through
the pore. The figure is only intended to convey the basic principle, and omits many
mechanistic and structural issues.
(Nature, 2005, Vol 433, 367-369)

Hydropathy plots identify potential -helical segments in a polypeptide chain

Two a helices in the aquaporin water channel, each of which spans only
halfway through the lipid bilayer

Converting a single-chain multipass protein into a two-chain multipass protein

Steps in the folding of a multipass transmembrane protein

An alternative way for peptide bonds in the lipid bilayer to satisfy their
hydrogen-binding requirements is for multiple transmembrane strands
of polypeptide chains to be arranged as sheet in the form of a closed barrel

Many membrane proteins are glycosylated and have intrachain or interchain

disulfide bonds

The cell coat, or glycocalyx is the carbohydrate-rich zone on the cell surface
Likely functions
protect cells against mechanical and chemical damage
keep foreign objects and other cells at a distance

A simplified diagram of the cell coat (glycocalyx)

Membrane proteins can be solubilized and purified in detergents

Structure and function of detergent micelles

Solubilizing membrane proteins with a mild detergent

The use of mild detergents for solubilizing, purifying, and reconstituting

functional membrane systems

Bacteriorhodopsin is a proton pump that traverses the lipid bilayer as seven helices

The archaean Halobacterium salinarum showing patches of purple membrane

that contain bacteriorhodopsin molecules

The three-dimensional structure of a bacteriorhodopsin molecule

Membrane proteins often function as large complexes

The three-dimensional structure of the photosynthetic reaction center of the bacterium

Rhodopseudomonas viridis

Many membrane proteins diffuse in the plane of the membrane

Fluorescence recovery after photobleaching

Fluorescence loss in photobleaching

Plasma membrane proteins are restricted to particular membrane

domains

Three domains in the plasma membrane of a sperm cell

Four ways of restricting the lateral mobility of specific plasma

membrane proteins

The cytosolic side of plasma membrane proteins can be studied in red blood
cell ghosts

The spectrin-based cytoskeleton on the cytosolic side of the human RBC membrane