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

channels and the electrical PROPERTIES of membranes
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In most vertebrate cells, an ABC transporter in the endoplasmic reticulum
(ER) membrane (named transporter associated with antigen processing, or TAP
transporter) actively pumps a wide variety of peptides from the cytosol into the
ER lumen. These peptides are produced by protein degradation in proteasomes
(discussed in Chapter 6). They are carried from the ER to the cell surface, where
they are displayed for scrutiny by cytotoxic T lymphocytes, which kill the cell if the
peptides are derived from a virus or other microorganism lurking in the cytosol of
an infected cell (discussed in Chapter 24).
Yet another member of the ABC transporter family is the cystic fibrosis transmembrane
conductance regulator protein (CFTR), which was discovered through
studies of the common genetic disease cystic fibrosis. This disease is caused by
a mutation in the gene encoding CFTR, a Cl – transport protein in the plasma
membrane of epithelial cells. CFTR regulates ion concentrations in the extracellular
fluid, especially in the lung. One in 27 Caucasians carries a gene encoding
a mutant form of this protein; in 1 in 2900, both copies of the gene are mutated,
causing the disease. In contrast to other ABC transporters, ATP binding and
hydrolysis in the CFTR protein do not drive the transport process. Instead, they
control the opening and closing of a continuous channel, which provides a passive
conduit for Cl – to move down its electrochemical gradient. Thus, some ABC
proteins can function as transporters and others as gated channels.
Summary
Transporters bind specific solutes and transfer them across the lipid bilayer by
undergoing conformational changes that alternately expose the solute-binding site
on one side of the membrane and then on the other. Some transporters move a single
solute “downhill,” whereas others can act as pumps to move a solute “uphill”
against its electrochemical gradient, using energy provided by ATP hydrolysis, by a
downhill flow of another solute (such as Na + or H + ), or by light to drive the requisite
series of conformational changes in an orderly manner. Transporters belong to a
small number of protein families. Each family evolved from a common ancestral
protein, and its members all operate by a similar mechanism. The family of P-type
transport ATPases, which includes Ca 2+ and Na + -K + pumps, is an important example;
each of these ATPases sequentially phosphorylates and dephosphorylates itself
during the pumping cycle. The superfamily of ABC transporters is the largest family
of membrane transport proteins and is especially important clinically. It includes
proteins that are responsible for cystic fibrosis, for drug resistance in both cancer
cells and malaria-causing parasites, and for pumping pathogen-derived peptides
into the ER for cytotoxic lymphocytes to reorganize on the surface of infected cells.
CHANNELS AND THE ELECTRICAL PROPERTIES
OF MEMBRANES
Unlike transporters, channels form pores across membranes. One class of channel
proteins found in virtually all animals forms gap junctions between adjacent
cells; each plasma membrane contributes equally to the formation of the channel,
which connects the cytoplasm of the two cells. These channels are discussed
in Chapter 19 and will not be considered further here. Both gap junctions and
porins, the channels in the outer membranes of bacteria, mitochondria, and chloroplasts
(discussed in Chapter 10), have relatively large and permissive pores, and
it would be disastrous if they directly connected the inside of a cell to an extracellular
space. Indeed, many bacterial toxins do exactly that to kill other cells (discussed
in Chapter 24).
In contrast, most channels in the plasma membrane of animal and plant cells
that connect the cytosol to the cell exterior necessarily have narrow, highly selective
pores that can open and close rapidly. Because these proteins are concerned
specifically with inorganic ion transport, they are referred to as ion channels. For
transport efficiency, ion channels have an advantage over transporters, in that