Biochemistry I   Spring & Fall Terms

ATP Synthase: Overall Architecture

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  Distances (Å)
      Heights
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      Subunit Labels

  Top View (F1)

  Proton Transfer Steps (Fo)
  1. Resting State
  2. Protonate Asp 61
  3. Deprotonate Asp 61
  4. Return to Resting State

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Structure of the ATP Synthase F1Fo Complex
This model is a composite from several published structures. However, it corresponds primarily to the bovine heart mitochondrial complex. (See note 2 below for comparison to the bacterial enzyme.) The intermembrane space is at the bottom; the matrix is at the top. The approximate plane of the inner mitochondrial membrane is indicated by the "Membrane Thickness" button.
The F1 portion of the model is shown as cartoons. The subunits shown are:
The globular (ab)3 ATPase. The three catalytic sites are in the b subunits (yellow) at the intefrace with the a subunits (red).
The g subunit (cyan) is an antiparallel a-helical coiled-coil. It extends downward from the center of the (ab)3 assembly to join with the d (dark green) and e (magenta) subunits. These three subunits are the central stalk that rotate with the ring of 10-12 Fo c subunits.
Overall dimensions are shown by the "Heights" button. The entire F1 is about 130 Å high; the membrane-embedded Fo is about 60 Å.
The Fo portion of the model is shown as Backbone. The partial complex shown is composed of 10 c subunits and the membrane-spanning helices of subunit a (green). Each c subunit has two membrane-spanning a-helices. The N-terminal helix faces the inside of the ring; the C-terminal helix is at the periphery. Asp 61 (at the middle of the C-terminal helices) are colored CPK. The single subunit with a deprotonated Asp 61 is colored blue. The nine subunits with protonated Asp 61 residues are colored red.
The ring model and its association with subunit a are modeled extensions of the structure determinations. See Rastogi & Girvin for details.
Not shown here is the dimeric subunit b that connects subunit a to the top of F1 complex. Subunit b is proposed to act as a "stator" for the motor, i.e. preventing rotation of the a3b3 domain as the g subunit rotates.
Top View: The view is from the mitochondrial matrix space. Only subunits a, b, and g are shown, colored as above. ATP, ADP, and Mg2+ are shown Spacefill, colored CPK. The catalytic b subunits are labeled "b-TP", "b-DP", and "b-E", corresponding respectively to "tight", "loose", and "open" (or empty) affinity for nucleotides. The noncatalytic a subunits are labeled "a-TP", "a-DP", and "a-E", corresponding to the b subunit with which they interact.
Rotation of the g subunit (along with the rest of the stalk and the Fo ring) in 120° steps causes the ab pairs to change conformation from: loose (ADP + Pi binding); to tight (ATP synthesis); to open (ATP dissociation into the matrix).
The essential rotational motion is driven by the flow of protons down an electrochemical gradient at a specific site in the Fo complex.
Proton Transfer Steps: The numbered buttons show a plausible series of H+ transfers at the Fo active site. The displays are based on the descriptions of Rastogi & Girvin and include conformational changes in the "blue" subunit. One sequence of steps would result in a 36° rotation of the subunit c ring. The rotation is not shown here. Thus, three (or four) H+ transfers are required to synthesize each ATP in F1.
1. Resting State: Subunit a, with Arg 210 indicated, and the 10 c subunits are shown with active site Asp 61 side chains. Arg 210 is known to be involved in the proton transfer. The subunit containing the active site Asp 61 ("COO-") is colored blue. All other Asp 61 residues are protonated (red subunits). Protons at high concentration in the intermembrane space are indicated by a single Spacefilled H+, labeled "H+ (out)".
2. Protonate Asp 61: "H+ (out)" moves into Fo and converts the active site Asp 61 to ("COOH"); the subunit changes conformation (and becomes a red subunit). Rotation of the subunit c ring is thought to be coupled to this step.
3. Deprotonate Asp 61: The H+ dissociates from Asp 61 ("COO-") and goes into the matrix as "H+ (in)".
4. Return to Resting State: The newly deprotonated blue subunit is reconverted back to the deprotonated conformation.
Notes
1. Each of the buttons leaves the highlighted features "selected" to permit a choice of additional display or coloring from the Chime menu.
2. For the homologous bacterial enzyme, simply substitute "periplasmic space" for "intermembrane space" and "cytosol" for "matrix space" in the above descriptions. In addition, the mitochondrial d subunit is called, e in the bacterial literature. Estimates of the number of c subunits in the Fo ring range from 9-12. The differences observed may reflect actual in vivo variability.
3. Coordinates assembled: The F1 complex has protein backbone atoms and the nucleotides in 1E79.pdb (bovine). Eight of the red subunits c have only Ca atoms taken from 1QO1.pdb (yeast). The other c subunits and subunit a have backbone atoms and several side chains from 1C17.pdb and 1C0V.pdb (E. coli).
4. Additional structural features of the Fo model are described on the ATP Synthase: Fo Structures page.
Details of the proton transfer mechanism proposed by Rastogi & Girvin are depicted on a separate page, ATP Synthase: Fo Proton Transfers.

The overall architecture of the F1Fo complex is described by:
Stock D, Leslie AG, Walker JE. (1999) "Molecular architecture of the rotary motor in ATP synthase." Science 286: 1700     PubMed [1QO1.pdb]
The structure of the F1 complex is described by:
Gibbons C, Montgomery MG, Leslie AG, Walker JE. (2000) "The structure of the central stalk in bovine F1-ATPase at 2.4 Å resolution." Nat Struct Biol 7: 1055     PubMed [1E79.pdb]
The NMR structure of unprotonated subunit c (pH 8) is described by:
Rastogi VK & Girvin ME. (1999) "Structural changes linked to proton translocation by subunit c of the ATP synthase." Nature 402: 263     PubMed [1C99.pdb]
This paper also described a model for the Fo ring-subunit a complex. [1C17.pdb & 1COV.pdb]

Back to the Protein Structure List.

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8.21.04