ATP is the cell’s “energy currency,” powering almost every chemical reaction. ATP synthase, embedded in the inner mitochondrial membrane, uses a proton gradient (proton-motive force) to rotate and produce ATP. Boyer proposed the binding-change mechanism, in which the β-subunits cycle through “open, loose, tight” states, while Walker solved X-ray crystal structures that revealed the enzyme’s 3-D arrangement. Together they showed how chemical energy and mechanical motion are coupled, providing a foundation for understanding respiration, photosynthesis and many other life processes.

Boyer’s binding-change model posits that the three β-subunits of the F1 domain exist in different conformations and are sequentially converted by rotation of the central γ-shaft. Walker solved the bovine heart mitochondrial F1-ATPase at 2.8 Å resolution, revealing the α3β3γδε architecture and the asymmetry among β-subunits. Subsequent cryo-EM studies visualized c-ring rotation in the F0 motor and identified proton pathways that support the chemiosmotic theory, firmly establishing the rotary catalytic mechanism at molecular detail. This knowledge informs drug design against bacterial ATP synthase, cancer metabolism, and the engineering of artificial nano-motors.

Boyer formalized the chemo-mechanical coupling of ATP synthase by proposing cooperative conformational changes of the β-subunits driven by 120° γ-shaft rotation. Walker solved multiple F1 complexes—MgADP-AlF4-, AMPPCP-bound, etc.—clarifying the spatial arrangement of the canonical P-loop NTPase motifs (Walker A/B) and the catalytic Lys. Subsequent structures resolved c10–15 rings and the a-subunit half channels, elucidating torque generation under ΔpH at near-quantum efficiency. Recent single-molecule FRET and high-speed AFM visualized 80° + 40° sub-steps and reverse rotation in real time, providing dynamic validation of the Boyer–Walker model.