Regulation of the thermoalkaliphilic F1-ATPase from Caldalkalibacillus thermarum.

ABSTRACT: The crystal structure has been determined of the F1-catalytic domain of the F-ATPase from Caldalkalibacillus thermarum, which hydrolyzes adenosine triphosphate (ATP) poorly. It is very similar to those of active mitochondrial and bacterial F1-ATPases. In the F-ATPase from Geobacillus stearothermophilus, conformational changes in the ?-subunit are influenced by intracellular ATP concentration and membrane potential. When ATP is plentiful, the ?-subunit assumes a "down" state, with an ATP molecule bound to its two C-terminal ?-helices; when ATP is scarce, the ?-helices are proposed to inhibit ATP hydrolysis by assuming an "up" state, where the ?-helices, devoid of ATP, enter the ?3?3-catalytic region. However, in the Escherichia coli enzyme, there is no evidence that such ATP binding to the ?-subunit is mechanistically important for modulating the enzyme's hydrolytic activity. In the structure of the F1-ATPase from C. thermarum, ATP and a magnesium ion are bound to the ?-helices in the down state. In a form with a mutated ?-subunit unable to bind ATP, the enzyme remains inactive and the ?-subunit is down. Therefore, neither the ?-subunit nor the regulatory ATP bound to the ?-subunit is involved in the inhibitory mechanism of this particular enzyme. The structure of the ?3?3-catalytic domain is likewise closely similar to those of active F1-ATPases. However, although the ?E-catalytic site is in the usual "open" conformation, it is occupied by the unique combination of an ADP molecule with no magnesium ion and a phosphate ion. These bound hydrolytic products are likely to be the basis of inhibition of ATP hydrolysis.

SUBMITTER: Ferguson SA 

PROVIDER: S-EPMC5047172 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature