Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

610 Chapter 11: Membrane Transport of Small Molecules and the Electrical Properties of Membranes
25 nm
outer lipid
bilayer
periplasmic
space
inner lipid
bilayer
CYTOSOL
lipopolysaccharide
porin
lipoprotein
peptidoglycan
soluble protein in
periplasmic space
ABC transporter
The first eukaryotic ABC transporters identified were discovered because of
their ability to pump hydrophobic drugs out of the cytosol. One of these transporters
is the multidrug resistance (MDR) MBoC6 protein, m11.18/11.17
also called P-glycoprotein. It is
present at elevated levels in many human cancer cells and makes the cells simultaneously
resistant to a variety of chemically unrelated cytotoxic drugs that are
widely used in cancer chemotherapy. Treatment with any one of these drugs can
result in the selective survival and overgrowth of those cancer cells that express an
especially large amount of the MDR transporter. These cells pump drugs out of the
cell very efficiently and are therefore relatively resistant to the drugs’ toxic effects
(Movie 11.5). Selection for cancer cells with resistance to one drug can thereby
lead to resistance to a wide variety of anticancer drugs. Some studies indicate that
up to 40% of human cancers develop multidrug resistance, making it a major hurdle
in the battle against cancer.
A related and equally sinister phenomenon occurs in the protist Plasmodium
falciparum, which causes malaria. More than 200 million people are infected
worldwide with this parasite, which remains a major cause of human death,
killing almost a million people every year. The development of resistance to the
antimalarial drug chloroquine has hampered the control of malaria. The resistant
P. falciparum have amplified a gene encoding an ABC transporter that pumps out
the chloroquine.
Figure 11–17 A small section of
the double membrane of an E. coli
bacterium. The inner membrane is
the cell’s plasma membrane. Between
the inner and outer membranes is a
highly porous, rigid peptidoglycan layer,
composed of protein and polysaccharide
that constitute the bacterial cell wall. It is
attached to lipoprotein molecules in the
outer membrane and fills the periplasmic
space (only a little of the peptidoglycan
layer is shown). This space also contains
a variety of soluble protein molecules. The
dashed threads (shown in green) at the
top represent the polysaccharide chains of
the special lipopolysaccharide molecules
that form the external monolayer of the
outer membrane; for clarity, only a few
of these chains are shown. Bacteria with
double membranes are called Gramnegative
because they do not retain the
dark blue dye used in Gram staining.
Bacteria with single membranes (but
thicker peptidoglycan cell walls), such as
staphylococci and streptococci, retain
the blue dye and are therefore called
Gram-positive; their single membrane is
analogous to the inner (plasma) membrane
of Gram-negative bacteria.
solute
OUTER
MEMBRANE
CELL EXTERIOR
porin
PERIPLASMIC
SPACE
periplasmic substratebinding
protein with
bound solute
solute-free periplasmic
substrate-binding
protein
INNER
(PLASMA)
MEMBRANE
CYTOSOL
ABC transporter
Figure 11–18 The auxiliary transport
system associated with transport
ATPases in bacteria with double
membranes. The solute diffuses through
channel proteins (porins) in the outer
membrane and binds to a periplasmic
substrate-binding protein that delivers it to
the ABC transporter, which pumps it across
the plasma membrane. The peptidoglycan
is omitted for simplicity; its porous structure
allows the substrate-binding proteins and
water-soluble solutes to move through it by
diffusion.