Regulation of the F1F0-ATP Synthase Rotary Nanomotor in its Monomeric-Bacterial and Dimeric-Mitochondrial Forms

Abstract

The F 1 F 0 -adenosine triphosphate (ATP) synthase rotational motor synthesizes most of the ATP required for living from adenosine diphosphate, Pi, and a proton electrochemical gradient across energy-transducing membranes of bacteria, chloroplasts, and mitochondria. However, as a reversible nanomotor, it also hydrolyzes ATP during de-energized conditions in all energy-transducing systems. Thus, different subunits and mechanisms have emerged in nature to control the intrinsic rotation of the enzyme to favor the ATP synthase activity over its opposite and commonly wasteful ATPase turnover. Recent advances in the structural analysis of the bacterial and mitochondrial ATP synthases are summarized to review the distribution and mechanism of the subunits that are part of the central rotor and regulate its gyration. In eubacteria, the ε subunit works as a ratchet to favor the rotation of the central stalk in the ATP synthase direction by extending and contracting two α-helixes of its C-terminal side and also by binding ATP with low affinity in thermophilic bacteria. On the other hand, in bovine heart mitochondria, the so-called inhibitor protein (IF 1 ) interferes with the intrinsic rotational mechanism of the central γ subunit and with the opening and closing of the catalytic β-subunits to inhibit its ATPase activity. Besides its inhibitory role, the IF 1 protein also promotes the dimerization of the bovine and rat mitochondrial enzymes, albeit it is not essential for dimerization of the yeast F 1 F 0 mitochondrial complex. High-resolution electron microscopy of the dimeric enzyme in its bovine and yeast forms shows a conical shape that is compatible with the role of the ATP synthase dimer in the formation of tubular the cristae membrane of mitochondria after further oligomerization. Dimerization of the mitochondrial ATP synthase diminishes the rotational drag of the central rotor that would decrease the coupling efficiency between rotation of the central stalk and ATP synthesis taking place at the F 1 portion. In addition, F 1 F 0 dimerization and its further oligomerization also increase the stability of the enzyme to natural or experimentally induced destabilizing conditions.

The Inhibitory Mechanism of the ζ Subunit of the F1FO-ATPase Nanomotor of Paracoccus denitrificans and Related α-Proteobacteria

“…This initial entrance of the subunit does not seem to be the final inhibitory position because the productive interaction of with PdF 1 -ATPase is enhanced by the catalytic turnover of the enzyme, similar to the mechanism described for the mitochondrial IF 1 . In this mechanism, some ATP hydrolysis turnovers are required for the proper binding of the inhibitor into its final inhibitory position (6,7,25).…”

“…Taken together, these antecedents supported the possibility that the inhibitory N-terminal domain of the subunit will also bind to the same ␣ DP /␤ DP /␥ interface as the inhibitory domains of ⑀ and IF 1 . In order to assess this hypothesis, the N-terminal inhibitory domain of (-NT) was aligned structurally with the mitochondrial IF 1 bound in its inhibitory position in the mitochondrial IF 1 .…”

“…The other side of , containing four ␣-helixes, works as a globular anchoring domain (7). These studies also showed cross-linking of with the ␣ and ␤ subunits of the F 1 -ATPase stator and with the ␥ and ⑀ subunits of the rotor, indicating that blocks rotation of the central stalk in a similar way to the mitochondrial IF 1 , which also blocks the intrinsic rotation of the mitochondrial F 1 -ATPase (8). The subunit also has a low affinity ATP binding site that seems to control its inhibitory capacity (7,9).…”

“…In order to prevent the reverse F 1 F OATPase activity, a couple of natural inhibitors have evolved: the eubacterial ⑀ subunit and the mitochondrial inhibitor protein (IF 1 ) 2 (reviewed in Ref. 1). Both inhibitors act to hinder predominantly the counterclockwise rotor gyration of the F 1 F OATPase (F 1 -ATPase turnover) by interacting differently with the ␥, ␣, and ␤ subunits (2)(3)(4).…”

Biological physics in México

“…Although institutions like the Instituto de Fisiología Celular [30][31][32] at UNAM and the Center for Research and Advanced Studies (Cinvestav) offer graduate programs in biophysics, their emphasis is more in the biological side of the subject [32,33]. With regards to BP, Cinvestav's physics department is already developing a research core [34][35][36][37][38][39], which other departments at Cinvestav are also doing research in biological physics and related issues [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]. We also should account for the work at the biophysics group in the Instituto de Física y Matemáticas of the Universidad Michoacana San Nicolás Hidalgo [58], as well as the Instituto de Ciencias Físicas [59][60][61][62][63][64][65][66][67][68][69][70][71][72], Instituto de Física [73]…”