The number of protons involved in ATP synthesis has been actively discussed and still is not resolved. Early measurements yielded a ratio of
protons transferred for ATP synthesized of 3H
+
/ATP, but other measurements have yielded 4H
+
/ATP and 4.67H
+
/ATP.
The coupling of proton transfer and ATP synthesis occurs in the enzyme
ATP synthase. This enzyme is a large multisubunit complex that has been
studied by many groups, most notably John Walker and Paul Boyer who
received the Nobel Prize for Chemistry in 1997 for their efforts (Abrahams
et al. 1994; Boyer 2000). The complex has two domains, identified as F 0
and F 1 , with the chloroplast enzyme domains denoted by CF 0 and CF 1 .
ATP synthase enzymes from different cells have a similar composition and
structure. The F 1 domain has three copies of the α and β subunits and
one copy of the other F 1 subunits δ, γ, and ε. The composition of the F 0
domain differs in different organisms, with the bacterial and mitochondrial
enzymes having one copy of the a subunit, two copies of the b subunit
(or an analogous subunit), and 10–14 copies of the c subunit.
The three-dimensional structure of the F 1 domain showed that the α
and β subunits are in an approximate hexameric arrangement but with
each subunit exhibiting a different conformation that reflects the three
different functional states: with ATP bound, with ADP bound, and with the
binding site empty (Figure 6.13). At the center is the single γ subunit that
forms a long, bent helical structure in the center of the structure. The γ
subunit is asymmetrically placed in the structure and interacts with only
one of the three β subunits.
The γ subunit extends below the F 1 domain
into the region of the F 0 domain. The F 0
domain is composed of three protein subunits,
a, b, and c. The c subunit is very hydrophobic
and consists of two transmembrane helices
with small loops. The c subunits are arranged
symmetrically around the F 1 symmetry axis
with the two sets of helices forming two
concentric circles (Figure 6.14; Meier et al.
2005; Murata et al. 2005). The rings of c
subunits are thought to be tightly associated
with the γ subunit of the F 1 domain but
not with the other subunits. In a motor, the
stator is stationary and the rotor spins in the
center. The c subunits can be considered to
form a rotor that can move independently of
the remaining portions of the protein that
would be the stator.
The rotation of the subunits was demonstrated by experiments performed by
Masamiysu Yoshida and Kazuhiko Kinosita
CHAPTER 6
REDOX REACTIONS AND BIOENERGETICS
129
α-ADP
α-ATP
β-ADP
β-ADP
β-empty
α-empty
Figure 6.13 Structure of the mitochondrial ATP
synthase F 1 domain viewed down the approximate
6-fold symmetry axis of the α and β subunits with
structural differences due to the ATP/ADP binding,
as indicated. At the center is the γ subunit. Based
upon Abrahams et al. (1994).
9781405124362_4_006.qxd 4/29/08 14:07 Page 129
protons transferred for ATP synthesized of 3H
+
/ATP, but other measurements have yielded 4H
+
/ATP and 4.67H
+
/ATP.
The coupling of proton transfer and ATP synthesis occurs in the enzyme
ATP synthase. This enzyme is a large multisubunit complex that has been
studied by many groups, most notably John Walker and Paul Boyer who
received the Nobel Prize for Chemistry in 1997 for their efforts (Abrahams
et al. 1994; Boyer 2000). The complex has two domains, identified as F 0
and F 1 , with the chloroplast enzyme domains denoted by CF 0 and CF 1 .
ATP synthase enzymes from different cells have a similar composition and
structure. The F 1 domain has three copies of the α and β subunits and
one copy of the other F 1 subunits δ, γ, and ε. The composition of the F 0
domain differs in different organisms, with the bacterial and mitochondrial
enzymes having one copy of the a subunit, two copies of the b subunit
(or an analogous subunit), and 10–14 copies of the c subunit.
The three-dimensional structure of the F 1 domain showed that the α
and β subunits are in an approximate hexameric arrangement but with
each subunit exhibiting a different conformation that reflects the three
different functional states: with ATP bound, with ADP bound, and with the
binding site empty (Figure 6.13). At the center is the single γ subunit that
forms a long, bent helical structure in the center of the structure. The γ
subunit is asymmetrically placed in the structure and interacts with only
one of the three β subunits.
The γ subunit extends below the F 1 domain
into the region of the F 0 domain. The F 0
domain is composed of three protein subunits,
a, b, and c. The c subunit is very hydrophobic
and consists of two transmembrane helices
with small loops. The c subunits are arranged
symmetrically around the F 1 symmetry axis
with the two sets of helices forming two
concentric circles (Figure 6.14; Meier et al.
2005; Murata et al. 2005). The rings of c
subunits are thought to be tightly associated
with the γ subunit of the F 1 domain but
not with the other subunits. In a motor, the
stator is stationary and the rotor spins in the
center. The c subunits can be considered to
form a rotor that can move independently of
the remaining portions of the protein that
would be the stator.
The rotation of the subunits was demonstrated by experiments performed by
Masamiysu Yoshida and Kazuhiko Kinosita
CHAPTER 6
REDOX REACTIONS AND BIOENERGETICS
129
α-ADP
α-ATP
β-ADP
β-ADP
β-empty
α-empty
Figure 6.13 Structure of the mitochondrial ATP
synthase F 1 domain viewed down the approximate
6-fold symmetry axis of the α and β subunits with
structural differences due to the ATP/ADP binding,
as indicated. At the center is the γ subunit. Based
upon Abrahams et al. (1994).
9781405124362_4_006.qxd 4/29/08 14:07 Page 129