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

THE PROTON PUMPS OF THE ELECTRON-TRANSPORT CHAIN
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(A)
membrane arm
(B)
H + H + H + H + CRISTA
SPACE
QH 2
Q
MATRIX
ubiquinone
amphipathic
helix
matrix
arm
iron–sulfur
clusters
FMN
2 e –
(C)
NADH NAD +
Figure 14–20 The structure of NADH dehydrogenase. (A) The model of the mitochondrial complex shown here is based on
the x-ray structure of the smaller bacterial complex, which works in the same way. The matrix arm of NADH dehydrogenase
(also known as Complex I) contains eight iron–sulfur (FeS) clusters that appear to participate in electron transport. The
membrane contains more than 70 transmembrane helices, forming three distinct proton-pumping modules, while the matrix arm
contains the electron-transport cofactors. (B) NADH donates two electrons, via a bound flavin mononucleotide (FMN; yellow),
to a chain of seven iron–sulfur clusters (red and yellow spheres). From the terminal iron–sulfur cluster, the electrons pass to
ubiquinone (orange). Electron transfer results in conformational changes (black arrows) that are thought to be transmitted to a
long amphipathic α helix (purple) on the matrix side of the membrane arm, which pulls on discontinuous transmembrane helices
(red) in three membrane subunits, each of which resembles an antiporter (see Chapter 11). This movement is thought to change
the conformation of charged residues in the three proton channels, resulting in the translocation of three protons out of the
matrix. A fourth proton may be translocated at the interface of the two arms (dotted line). (C) This shows the symbol for NADH
dehydrogenase used throughout this chapter. (Adapted from R.G. Efremov, R. Baradaran and L.A. Sazanov, Nature
465:441–445, 2010. PDB code: 3M9S.)
MBoC6 n14.307/14.20
the respiratory chain, ubiquinol tranfers electrons from NADH dehydrogenase to
cytochrome c reductase. Because the protons in this QH 2 molecule are taken up
from the matrix and released on the opposite side of the crista membrane, two
protons are transferred from the matrix into the crista space per pair of electrons
transferred (Figure 14–21). This vectorial transfer of protons supplements the
electrochemical proton gradient that is created by the NADH dehydrogenase proton
pumping just discussed.
Cytochrome c reductase is a large assembly of membrane protein subunits.
Three subunits form a catalytic core that passes electrons from ubiquinol to
cytochrome c, with a structure that has been highly conserved from bacterial
ancestors (Figure 14–22). It pumps protons by a vectorial transfer of protons
that involves a binding site for a second molecule of ubiquinone; the elaborate
CRISTA SPACE
MATRIX
Q
NADH
dehydrogenase
QH 2
2 H +
2 H +
Q
QH 2
cytochrome c
reductase
Figure 14–21 How a directional release
and uptake of protons by a quinone
pumps protons across a membrane.
Two protons are picked up on the matrix
side of the inner mitochondrial membrane
when the reaction Q + 2e – + 2H + → QH 2
is catalyzed by the NADH dehydrogenase
complex. This molecule of ubiquinol
(QH 2 ) diffuses rapidly in the plane of the
membrane, becoming bound to the crista
side of cytochrome c reductase. When
its oxidation by cytochrome c reductase
generates two protons and two electrons
(see Figure 14–17), the two protons are
released into the crista space. The flow of
electrons is not shown in this diagram.