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

604 Chapter 11: Membrane Transport of Small Molecules and the Electrical Properties of Membranes
(A)
Na +
N
leucine
C
N
(B)
pseudosymmetric conserved core
Some other types of important membrane transport proteins are also built from
inverted repeats. Examples even include channel proteins such as the aquaporin
water channel (discussed later) and the Sec61 channel through which nascent
polypeptides move into the endoplasmic MBoC6 n11.150/11.10 reticulum (discussed in Chapter 12). It
is thought that these channels evolved from coupled transporters, in which the
gating functions were lost, allowing them to open toward both sides of the membrane
simultaneously to provide a continuous path across the membrane.
In bacteria, yeasts, and plants, as well as in many membrane-enclosed organelles
of animal cells, most ion-driven active transport systems depend on H +
rather than Na + gradients, reflecting the predominance of H + pumps in these
membranes. An electrochemical H + gradient across the bacterial plasma membrane,
for example, drives the inward active transport of many sugars and amino
acids.
C
Figure 11–10 Transporters are built from
inverted repeats. (A) LeuT, a bacterial
leucine/Na + symporter related to human
neurotransmitter transporters, such as the
serotonin transporter, is shown. The core
of the transporter is built from two bundles,
each composed of five α helices (blue
and yellow). The helices shown in gray
differ among members of this transporter
family and are thought to play regulatory
roles, which are specific to a particular
transporter. (B) Both core helix bundles are
packed in a similar arrangement (shown
as a hand, with the broken helix as the
thumb), but the second bundle is inverted
with respect to the first. The transporter’s
structural pseudosymmetry reflects its
functional symmetry: the transporter can
work in either direction, depending on the
direction of the ion gradient. (Adapted from
K.R. Vinothkumar and R. Henderson,
Q. Rev. Biophys. 43:65–158, 2010. With
permission from Cambridge University
Press. PDB code: 3F3E.)
Transporters in the Plasma Membrane Regulate Cytosolic pH
Most proteins operate optimally at a particular pH. Lysosomal enzymes, for
example, function best at the low pH (~5) found in lysosomes, whereas cytosolic
enzymes function best at the close-to-neutral pH (~7.2) found in the cytosol. It
is therefore crucial that cells control the pH of their intracellular compartments.
Most cells have one or more types of Na + -driven antiporters in their plasma
membrane that help to maintain the cytosolic pH at about 7.2. These transporters
use the energy stored in the Na + gradient to pump out excess H + , which either
leaks in or is produced in the cell by acid-forming reactions. Two mechanisms are
used: either H + is directly transported out of the cell or HCO
– 3 is brought into the
cell to neutralize H + in the cytosol (according to the reaction HCO
– 3 + H + → H 2 O +
CO 2 ). One of the antiporters that uses the first mechanism is a Na + –H + exchanger,
which couples an influx of Na + to an efflux of H + . Another, which uses a combination
of the two mechanisms, is a Na + -driven Cl – –HCO
– 3 exchanger that couples
an influx of Na + and HCO
– 3 to an efflux of Cl – and H + (so that NaHCO 3 comes
in and HCl goes out). The Na + -driven Cl – –HCO
– 3 exchanger is twice as effective
as the Na + –H + exchanger: it pumps out one H + and neutralizes another for each
Na + that enters the cell. If HCO
– 3 is available, as is usually the case, this antiporter
is the most important transporter regulating the cytosolic pH. The pH inside the
cell regulates both exchangers; when the pH in the cytosol falls, both exchangers
increase their activity.
A Na + -independent Cl – –HCO
– 3 exchanger adjusts the cytosolic pH in the
reverse direction. Like the Na + -dependent transporters, pH regulates the Na + -independent
Cl – –HCO
– 3 exchanger, but the exchanger’s activity increases as the
cytosol becomes too alkaline. The movement of HCO
– 3 in this case is normally
out of the cell, down its electrochemical gradient, which decreases the pH of the