Insights into the regulatory function of the 1 subunit from bacterial F-type ATP synthases

Insights into the regulatory function of the 1 subunit from bacterial F-type ATP synthases: A comparison of structural, biochemical and biophysical data

Krah, Alexander (Korea Institute for Advanced Study)
Zarco-Zavala, Mariel (University of Tokyo)
McMillan, D.G.G. (TU Delft BT/Biocatalysis)

2018

ATP synthases catalyse the formation of ATP, the most common chemical energy storage unit found in living cells. These enzymes are driven by an electrochemical ion gradient, which allows the catalytic evolution of ATP by a binding change mechanism. Most ATP synthases are capable of catalysing ATP hydrolysis to varying degrees, and to prevent wasteful ATP hydrolysis, bacteria and mitochondria have regulatory mechanisms such as ADP inhibition. Additionally, 1 subunit inhibition has also been described in three bacterial systems, Escherichia coli, Bacillus PS3 and Caldalkalibacillus thermarum TA2.A1. Previous studies suggest that the 1 subunit is capable of undergoing an ATP-dependent conformational change from the ATP hydrolytic inhibitory ‘extended’ conformation to the ATP-induced non-inhibitory ‘hairpin’ conformation. A recently published crystal structure of the F₁ domain of the C. thermarum TA2.A1 F₁F_o ATP synthase revealed a mutant 1 subunit lacking the ability to bind ATP in a hairpin conformation. This is a surprising observation considering it is an organism that performs no ATP hydrolysis in vivo, and appears to challenge the current dogma on the regulatory role of the 1 subunit. This has prompted a re-examination of present knowledge of the 1 subunits role in different organisms. Here, we compare published biochemical, biophysical and structural data involving 1 subunit-mediated ATP hydrolysis regulation in a variety of organisms, concluding that the 1 subunit from the bacterial F-type ATP synthases is indeed capable of regulating ATP hydrolysis activity in a wide variety of bacteria, making it a potentially valuable drug target, but its exact role is still under debate.

1 subunit
Bacterial
F-type ATP synthases
Hydrolysis of ATP
Regulation

http://resolver.tudelft.nl/uuid:d75468ad-067f-440c-94f0-6a351dabfa76

https://doi.org/10.1098/rsob.170275

Open Biology, 8 (5)

Institutional Repository

review

© 2018 Alexander Krah, Mariel Zarco-Zavala, D.G.G. McMillan