ATP Synthase

ATP synthase is an amazing combination of enzyme, H⁺ transporter, and motor, all found in the inner mitochondrial membrane. This complicated protein consists of two main components, each containing several protein chains.

The H⁺ transporter component, known as F_o, is found in the inner mitochondrial membrane. To understand exactly how it functions, you need to know about three types of subunits: a, c, and γ.

Subunit a actually contains two half-channels; one is open to the P side of the membrane, and the other is open to the N side of the membrane. They aren't connected, though, so it isn't possible for H⁺ to move into the P half channel and then directly into the N half channel.

There is only one subunit a, but there are ten to twelve subunit c's, each consisting of an
α-helix. The c subunits form a ring within the plane of the membrane. You can imagine seeing them as a circle if you were looking down on the membrane. Each c subunit has an aspartate side chain that projects out of the circle into the membrane. The aspartate side chain is about half-way through the membrane, positioned so that it can enter the P half channel of the a subunit and pick up H⁺ and then move to the N half channel and release H⁺.  

That sounds as though moving H⁺ is a one-step process: pick up H⁺ from the P side, move to the N side channel and deliver H⁺, and H⁺ transport is done. In that case, though, no ATP would be made. Instead, when a c subunit picks up H⁺, which neutralizes the aspartate side chain, the subunit rotates into the membrane. In fact, the whole ring of c subunits rotates, and each c subunit, in turn, delivers H⁺ to the N side and then immediately picks up a new H⁺ from the P side.

In the diagram, subunit J has just delivered its H⁺ to the N side, and subunit A has just acquired a new H⁺ from the P side. The γ subunit associates with the ring of c subunits and also with the enzyme part of ATP synthase, which is in the matrix. Notice that when the ring of c subunits rotates, the γ subunit also rotates.

So far, this is just a way of getting H⁺ from one side of the membrane to the other, but no ATP has been synthesized. That is the responsibility of the other half of ATP synthase–F₁.

F₁ is in the matrix but connected with F_oso that when the ring of c subunits rotates, the F₁ subunits change conformation. F₁ consists of several subunits, but the most important are the β-subunits, which convert ADP + P_i to ATP + H₂O. There are three β subunits, and at any time, the three have three different conformations: open (O), loose (L), and tight (T).

The L conformation binds ADP and P_i and then is converted to the T conformation when the c ring and the γ subunit move. The T conformation converts the ADP and P_i to ATP, but, because the β subunit in the T conformation binds ATP very tightly, the ATP can't be released until the c ring and the γ subunit rotate again. Then the T conformation is converted to the O conformation, which releases the newly formed ATP.

This is easier to see if you focus on just one subunit at a time. Remember that changing the conformations of all the β subunits requires that the c ring rotate about a third of a rotation, which requires about 3 H⁺ moving through F_o.

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