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

PROTEIN FUNCTION
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which walks along actin filaments (Figure 3–75B), and the kinesin proteins that
walk along microtubules (both discussed in Chapter 16). These movements can
be rapid: some of the motor proteins involved in DNA replication (the DNA helicases)
propel themselves along a DNA strand at rates as high as 1000 nucleotides
per second.
Membrane-Bound Transporters Harness Energy to Pump
Molecules Through Membranes
We have thus far seen how proteins that undergo allosteric shape changes can act
as microprocessors (Src family kinases), as assembly factors (EF-Tu), and as generators
of mechanical force and motion (motor proteins). Allosteric proteins can
also harness energy derived from ATP hydrolysis, ion gradients, or electron-transport
processes to pump specific ions or small molecules across a membrane. We
consider one example here that will be discussed in more detail in Chapter 11.
The ABC transporters (ATP-binding cassette transporters) constitute an
important class of membrane-bound pump proteins. In humans, at least 48 different
genes encode them. These transporters mostly function to export hydrophobic
molecules from the cytoplasm, serving to remove toxic molecules at the
mucosal surface of the intestinal tract, for example, or at the blood–brain barrier.
The study of ABC transporters is of intense interest in clinical medicine, because
the overproduction of proteins in this class contributes to the resistance of tumor
cells to chemotherapeutic drugs. In bacteria, the same types of proteins primarily
function to import essential nutrients into the cell.
A typical ABC transporter contains a pair of membrane-spanning subunits
linked to a pair of ATP-binding subunits located just below the plasma membrane.
As in other examples we have discussed, the hydrolysis of the bound ATP
molecules drives conformational changes in the protein, transmitting forces that
cause the membrane-spanning subunits to move their bound molecules across
the lipid bilayer (Figure 3–76).
Humans have invented many different types of mechanical pumps, and it
should not be surprising that cells also contain membrane-bound pumps that
Figure 3–76 The ABC (ATP-binding
cassette) transporter, a protein machine
that pumps molecules through a
membrane. (A) How this large family of
transporters pumps molecules into the
cell in bacteria. As indicated, the binding
of two molecules of ATP causes the two
ATP-binding domains to clamp together
tightly, opening a channel to the cell exterior.
The binding of a substrate molecule to the
extracellular face of the protein complex then
triggers ATP hydrolysis followed by ADP
release, which opens the cytoplasmic gate;
the pump is then reset for another cycle.
(B) As discussed in Chapter 11, in
eukaryotes an opposite process occurs,
causing selected substrate molecules to be
pumped out of the cell. (C) The structure
of a bacterial ABC transporter (see Movie
11.5). (C, from R.J. Dawson and K.P. Locher,
Nature 443:180–185, 2006. With permission
from Macmillan Publishers Ltd;
PDB code: 2HYD).
(A) A BACTERIAL ABC TRANSPORTER (C)
small molecule
CYTOSOL
ATPase
domains
ATP ATP
2 ATP
2 ADP +
P i
(B)
A EUKARYOTIC ABC TRANSPORTER
CYTOSOL
ATPase
domains
ATP
ATP
small
molecule
2 ATP
2 ADP +
P i