A Normal Mode Analysis of Structural Plasticity in the Biomolecular Motor F1-ATPase

Normal modes have been used to explore the inherent flexibility of the α, β and γ subunits of F1-ATPase in isolation and as part of the α3β3γ complex. It was found that the structural plasticity of the γ and β subunits, in particular, correlates with their functions. The N and C-terminal helices forming the coiled-coil domain of the γ subunit are highly flexible in the isolated subunit, but more rigid in the α3β3γ complex due to interactions with other subunits. The globular domain of the γ subunit is structurally relatively rigid when isolated and in the α3β3γ complex; this is important for its functional role in coupling the F0 and F1 complex of ATP synthase and in inducing the conformational changes of the β subunits in synthesis. Most important, the character of the lowest-frequency modes of the βE subunit is highly correlated with the large βE→βTP transition. This holds for the C-terminal domain and the nucleotide-binding domain, which undergo significant conformational transitions in the functional cycle of F1-ATPase. This is most evident in the ligand-free βE subunit; the flexibility in the nucleotide-binding domain is reduced somewhat in the βTP subunit in the presence of Mg2+·ATP. The low-frequency modes of the α3β3γ complex show that the motions of the globular domain of the γ subunit and of the C-terminal and nucleotide binding domains of the βE subunits are coupled, in accord with their function. Overall, the normal mode analysis reveals that F1-ATPase, like other macromolecular assemblies, has the intrinsic structural flexibility required for its function encoded in its sequence and three-dimensional structure. This inherent plasticity is an essential aspect of assuring a small free energy cost for the large-scale conformational transition that occurs in molecular motors.