Abstract
V-ATPase is an energy converting enzyme, coupling ATP hydrolysis/synthesis in the hydrophilic V1 domain, with proton flow through the Vo membrane domain, via rotation of the central rotor complex relative to the surrounding stator apparatus. Upon dissociation from the V1 domain, the Vo domain of the eukaryotic V-ATPase can adopt a physiologically relevant auto-inhibited form in which proton conductance through the Vo domain is prevented, however the molecular mechanism of this inhibition is not fully understood. Using cryo-electron microscopy, we determined the structure of both the holo V/A-ATPase and isolated Vo at near-atomic resolution, respectively. These structures clarify how the isolated Vo domain adopts the auto-inhibited form and how the holo complex prevents formation of the inhibited Vo form.
Highlights
IntroductionRotary ATPase/ATP synthases, roughly classified into F type and V type ATPases, are marvelous, tiny rotary machines (Yokoyama and Imamura, 2005; Kinosita, 2012; Forgac, 2007; Yoshida et al, 2001; Kuhlbrandt, 2019)
Rotary ATPase/ATP synthases, roughly classified into F type and V type ATPases, are marvelous, tiny rotary machines (Yokoyama and Imamura, 2005; Kinosita, 2012; Forgac, 2007; Yoshida et al, 2001; Kuhlbrandt, 2019). These rotary motor proteins share a basic molecular architecture composed of a central rotor complex and surrounding stator apparatus. These proteins function to couple ATP hydrolysis/synthesis in the hydrophilic F1/V1 moiety with proton translocation through the membrane embedded hydrophobic Fo/Vo moiety by rotation of the central rotor complex relative to the surrounding stator apparatus, via a rotary catalytic mechanism (Figure 1; Kinosita, 2012; Forgac, 2007; Yoshida et al, 2001; Kuhlbrandt, 2019; Guo and Rubinstein, 2018)
These proteins function to couple ATP hydrolysis/synthesis in the hydrophilic F1/V1 moiety with proton translocation through the membrane embedded hydrophobic Fo/Vo moiety by rotation of the central rotor complex relative to the surrounding stator apparatus, via a rotary catalytic mechanism (Figure 1; Kinosita, 2012; Forgac, 2007; Yoshida et al, 2001; Kuhlbrandt, 2019; Guo and Rubinstein, 2018). Both F and V type ATPases are basically capable of either ATP synthesis coupled to the proton motive force driven by the membrane potential or proton pumping powered by ATP hydrolysis
Summary
Rotary ATPase/ATP synthases, roughly classified into F type and V type ATPases, are marvelous, tiny rotary machines (Yokoyama and Imamura, 2005; Kinosita, 2012; Forgac, 2007; Yoshida et al, 2001; Kuhlbrandt, 2019) These rotary motor proteins share a basic molecular architecture composed of a central rotor complex and surrounding stator apparatus. The V/A-ATPase from a thermophilic bacterium, Thermus thermophilus (Tth V/A-ATPase) is a rotary ATPase that has been well
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