Biomedical Engineering Reference
In-Depth Information
Fig. 2
Schematic representation of the structure of F
0
F
1
-ATP synthase. See text for details.
Reproduced by permission from Balzani et al.
2003
and inorganic phosphate, P
i
. When F
1
dominates, it hydrolyzes ATP and drives the
F
0
motor in reverse, turning it into an ion pump that moves ions across the mem-
brane against the electrochemical gradient. The mechanochemistry of ATP synthase
has been studied in great detail (Boyer
1993
; Rastogi and Girvin
1999
; Stock et al.
1999
; Oster and Wang
2000
; Ren and Allison
2000
; Seelert et al.
2000
; Bustamante
et al.
2001
; Frey
2002
;
2003
; Schliwa and Woehlke
2003
) and new structural infor-
mation continues to appear (Rondelez et al.
2005
) .
This enzyme consists of two principal domains (Fig.
2
). The asymmetric mem-
brane-spanning F
0
portion contains a proton channel, and the soluble F
1
portion
contains three catalytic sites which cooperate in the synthetic reactions. The cata-
lytic region is made up of nine protein subunits with the stoichiometry 3 a :3 b :1 g :1 d :1 e ,
approximating to a fl attened sphere, 10 nm across and 8 nm high. The fl ow of pro-
tons through F
0
generates a torque, which is transmitted to F
1
by an asymmetric
shaft, the g-subunit. This subunit acts as a rotating “cam” within F
1
, sequentially
releasing ATPs from the three active sites. The free energy difference across the
inner membrane of mitochondria and bacteria is suffi cient to produce 3 ATPs per 12
protons passing through the motor.
As mentioned above, the F
0
F
1
-ATP synthase is reversible, i.e., the full enzyme
can synthesize or hydrolyze ATP; F
1
in isolation, however, can only hydrolyze it. The
spinning of F
1
-ATP synthase, i.e., the rotary motor nature of this enzyme, was fi rst
