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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iron–sulfur
clusters
iron–sulfur
cluster
cytochrome c
copper
atom
Q
½O 2 H 2 O
cytochrome c
reductase
NADH NAD +
NADH dehydrogenase
cytochrome c
oxidase
CRISTA
SPACE
MATRIX
a molecule of ubiquinone. The reduced ubiquinol then passes its two electrons
to the respiratory chain via cytochrome c reductase (see Figure 14–18). Succinate
dehydrogenase is not MBoC6 a proton n14.312/14.26 pump, and it does not contribute directly to the
electrochemical potential utilized for ATP production in mitochondria. Thus, it is
not considered to be an integral part of the respiratory chain.
Protons Can Move Rapidly Through Proteins Along Predefined
Pathways
The protons in water are highly mobile: by rapidly dissociating from one water
molecule and associating with its neighbor, they can rapidly flit through a hydrogen-bonded
network of water molecules (see Figure 2–5). But how can a proton
move through the hydrophobic interior of a protein embedded in the lipid
bilayer? Proton-translocating proteins contain so-called proton wires, which are
rows of polar or ionic side chains, or water molecules spaced at short distances,
so that the protons can jump from one to the next (Figure 14–27). Along such
predefined pathways, protons move up to 40 times faster than through bulk water.
The three-dimensional structure of cytochrome c oxidase indicates two different
proton-uptake pathways. This confirmed earlier mutagenesis studies, which had
shown that replacing the side chains of particular aspartate or arginine residues,
whose side chains can bind and release protons, made the cytochrome c oxidase
less efficient as a proton pump.
But how can electron transport cause allosteric changes in protein conformations
that pump protons? From the most basic point of view, if electron transport
drives sequential allosteric changes in protein conformation that alter the redox
state of the components, these conformational changes can be connected to protein
wires that allow the protein to pump H + across the crista membrane. This
type of H + pumping requires at least three distinct conformations for the pump
protein, as schematically illustrated in Figure 14–28.
Figure 14–27 Proton movement through water and proteins. (A) Protons
move rapidly through water, hopping from one H 2 O molecule to the next
by the continuous formation and dissociation of hydronium ions, H 3 O + (see
Chapter 2). In this diagram, proton jumps are indicated by red arrows.
(B) Protons can move even more rapidly through a protein along “proton
wires.” These are predefined proton paths consisting of suitably spaced
amino acid side chains that accept and release protons easily (Asp, Glu)
or carry a waterlike hydroxyl group (Ser, Thr), along with water molecules
trapped in the protein interior.
Figure 14–26 The respiratory-chain
supercomplex from bovine heart
mitochondria. The three proton-pumping
complexes of the mitochondrial respiratory
chain of mammalian mitochondria
assemble into large supercomplexes in the
crista membrane. Supercomplexes can
be isolated by mild detergent treatment
of mitochondria, and their structure
has been deciphered by single-particle
cryoelectron microscopy. The bovine
heart supercomplex has a total mass of
1.7 megadaltons. Shown is a schematic
of such a complex that consists of
NADH dehydrogenase, cytochrome c
reductase, and cytochrome c oxidase, as
indicated. The facing quinol-binding sites
of NADH dehydrogenase and cytochrome
c reductase, plus the short distance
between the cytochrome c-binding sites in
cytochrome c reductase and cytochrome
c oxidase, facilitate fast, efficient electron
transfer. Cofactors active in electron
transport are marked as a yellow dot
(flavin mononucleotide), red and yellow
dots (iron–sulfur clusters), Q (quinone), red
squares (hemes), and a blue dot (copper
atom). Only cofactors participating in the
linear flow of electrons from NADH to water
are shown. Blue arrows indicate the path
of the electrons through the supercomplex.
(Adapted from T. Athoff et al., EMBO J.
30:4652–4664, 2011.)
(A)
H
H
H
H O
H + H O
O
H
H H H O H
O
O
H
H
H
O
O H +
H
H
O H H
H
(B)
O
O –
H
CH 2
H + H
H
H
CH 2
O
H
O
HO
H
O
O
H + H
H
O –
O
OH