ATP SynthaseDecember 2005 Molecule of the Month by David Goodsell
doi: 10.2210/rcsb_pdb/mom_2005_12 (PDF Version, ePub Version )
ATP synthase is one of the wonders of the molecular world. ATP synthase is an enzyme, a molecular motor, an ion pump, and another molecular motor all wrapped together in one amazing nanoscale machine. It plays an indispensable role in our cells, building most of the ATP that powers our cellular processes. The mechanism by which it performs this task is a real surprise.
ATP synthesis is composed of two rotary motors, each powered by a different fuel. The motor at the top, termed F0, an electric motor. It is embedded in a membrane (shown schematically as a gray stripe here), and is powered by the flow of hydrogen ions across the membrane. As the protons flow through the motor, they turn a circular rotor (shown in blue). This rotor is connected to the second motor, termed F1. The F1 motor is a chemical motor, powered by ATP. The two motors are connected together by a stator, shown on the right, so that when F0 turns, F1 turns too.
Motor to Generator
So why have two motors connected together? The trick is that one motor can force the other motor to turn, and in this way, change the motor into a generator. This is what happens in our cells: the F0 motor uses the power from a proton gradient to force the F1 motor to generate ATP. In our cells, food is broken down and used to pump hydrogen ions across the mitochondrial membrane. The F0 portion of ATP synthase allows these ions to flow back, turning the rotor in the process. As the rotor turns, it turns the axle and the F1 motor becomes a generator, creating ATP as it turns.
Large, complex molecular machines like ATP synthase pose
difficult problems for structural scientists, so the structures of these
machines are often determined in parts. The picture shown here is a composite of
four different structures, combining structures determined by X-ray
crystallography and NMR spectroscopy. The F0 motor is included in PDB file 1c17. The F1 motor
and the axle that connects the two are included in PDB file 1e79. The stator has
proven to be the most elusive part--the two pieces shown here are from PDB files
2a7u and 1l2p.
For information on ATP synthase from a genomics perspective, take a look at the Protein of the Month at the European Bioinformatics Institute.
Exploring the F1 Structure
PDB entry 1e79 includes the F1
motor of ATP synthase. When operating as a generator, it uses the power of
rotational motion to build ATP, or when operating as a motor, it breaks down ATP
to spin the axle the opposite direction. The synthesis of ATP requires several steps,
including the binding of ADP and phosphate, the formation of the new
phosphate-phosphate bond, and release of ATP. As the axle turns, it
forces the motor into three different conformations that assist these difficult
steps. Two states are shown here. The one on the left shows a conformation that
assists the binding of ADP, and the one on the right shows a conformation that
has been forced open to release ATP. Notice how the oddly-shaped axle forces the
change in conformation.
You can look at this structure yourself by clicking on the accession code and picking one of the options under View Structure. The central axle is composed of chains G, H, and I in this file. Three of the subunits, chains D, E, and F in the file, are the ATP-generating parts--subunit E is shown in red in the left picture and subunit D is shown in the right picture. Subunits A, B, and C are similar, but play a structural role, holding everything in place. In these pictures, I have removed the two nearest two subunits to make the interaction clearer.
Exploring the F0 Structure
PDB entry 1c17 includes the F0
electric motor. In this picture, we are looking down the axis of rotation, as if
we where looking down at the top of the picture on the first page. The rotor is
composed of 12 identical protein chains, colored blue here, and the ion pump is
a single chain, colored red. The pump has an arginine amino acid that hands off
a hydrogen ion to aspartates on the rotor. Aspartate amino acids typically have
a negative charge, but since the rotor is surrounded by membrane lipids, this
would be very unfavorable. So, the rotor only turns when the aspartates have a
hydrogen attached, neutralizing their charge. Hydrogen ions take a convoluted
path through the F0 motor, turning the rotor in the process. They are gathered
by a chain of amino acids in the pump, and transferred to the arginine.
The arginine passes the hydrogen to the rotor, which turns all the
way around. Then the hydrogen is offloaded by other amino acids on the pump,
and finally passed to the opposite side of the membrane.
The exact path of the hydrogen ions through the
pump is still a matter of intense study.
These pictures were created with RasMol. You can create similar pictures by clicking on the accession codes here and picking one of the options under View Structure.
Additional information on ATP synthase
P. D. Boyer (1997) The ATP
Synthase--A Splendid Molecular Machine. Annual Review of Biochemistry 66,
G. Oster and H. Wang (1999) ATP Synthase: Two Motors, Two Fuels. Structure 7, R67- R72.
G. Oster and H. Wang (2003) Rotary Protein Motors. Trends in Cell Biology 13, 114- 121.
© 2013 David Goodsell & RCSB Protein Data Bank