complex drive the rotation of the rotor ysclo subunits at about 100 Hz. This rotation,

which is absolutely essential for the machinery of the enzyme, transmits energy over a

distance greater than 100 A+ by providing the means by which conformational changes in

the Fl catalytic core, u3 3, take place for the synthesis of ATP (3, 4).

 Structural studies of F1Fo ATP synthase commenced in the early 1960's and persist

to this day in pursuit of a complete high-resolution structure. Negative staining

procedures in the early 1960's initially revealed the traditional tripartite features of the

enzyme complex from sub-mitochondrial particles, consisting of what was referred to as

the headpiece, stalk and basepiece (Figure 1-1) (17). Ten years later, the first electron

micrograph of a detergent-solubilized F1Fo ATP synthase was published, confirming the

existing idea of a tripartite molecule (18). Appreciably, electron microscopy (EM) in

combination with other biochemical data of isolated Fl exposed a hexagonal arrangement

of alternating subunits with a seventh mass found in the center of the array (Figure 1-1)

(7, 19). Based on this premise it was first suggested that Fl consisted of an alternating

hexagonal array of three a and three P subunits with the y, 6 and a situated centrally (7).

The idea did not gain favorable recognition for some twenty years until verified by x-ray

crystallography (20, 21). Continuous improvements in EM technology led to numerous

publications of various ATP synthases which defined the average overall dimensions of

about 190 A+ from top to bottom and about 37 A+ assigned to the stalk structure (22-25).

Using a combination of traditional biochemical, molecular biological and immunological

techniques along with EM, many important discoveries were made that led to what we

now understand of F1Fo ATP synthase. The first direct evidence for rotation of the stalk

appeared in 1990 (24), but was not followed by the visualization of the peripheral stalk,