Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 50 (5), 403-424

Control of Rotation of the F 1 F O-ATP Synthase Nanomotor by an Inhibitory α-Helix From Unfolded ε or Intrinsically Disordered ζ and IF 1 Proteins

Affiliations
Review

Control of Rotation of the F 1 F O-ATP Synthase Nanomotor by an Inhibitory α-Helix From Unfolded ε or Intrinsically Disordered ζ and IF 1 Proteins

Francisco Mendoza-Hoffmann et al. J Bioenerg Biomembr.

Abstract

The ATP synthase is a ubiquitous nanomotor that fuels life by the synthesis of the chemical energy of ATP. In order to synthesize ATP, this enzyme is capable of rotating its central rotor in a reversible manner. In the clockwise (CW) direction, it functions as ATP synthase, while in counter clockwise (CCW) sense it functions as an proton pumping ATPase. In bacteria and mitochondria, there are two known canonical natural inhibitor proteins, namely the ε and IF1 subunits. These proteins regulate the CCW F1FO-ATPase activity by blocking γ subunit rotation at the αDPDP/γ subunit interface in the F1 domain. Recently, we discovered a unique natural F1-ATPase inhibitor in Paracoccus denitrificans and related α-proteobacteria denoted the ζ subunit. Here, we compare the functional and structural mechanisms of ε, IF1, and ζ, and using the current data in the field, it is evident that all three regulatory proteins interact with the αDPDP/γ interface of the F1-ATPase. In order to exert inhibition, IF1 and ζ contain an intrinsically disordered N-terminal protein region (IDPr) that folds into an α-helix when inserted in the αDPDP/γ interface. In this context, we revised here the mechanism and role of the ζ subunit as a unidirectional F-ATPase inhibitor blocking exclusively the CCW F1FO-ATPase rotation, without affecting the CW-F1FO-ATP synthase turnover. In summary, the ζ subunit has a mode of action similar to mitochondrial IF1, but in α-proteobacteria. The structural and functional implications of these intrinsically disordered ζ and IF1 inhibitors are discussed to shed light on the control mechanisms of the ATP synthase nanomotor from an evolutionary perspective.

Keywords: ATP synthase; Instrisically disordered; Natural inhibitor; Paracoccus denitrificans; Pawl; Ratchet; ζ subunit.

Similar articles

See all similar articles

Cited by 2 articles

References

    1. J Basic Microbiol. 2004;44(1):17-22 - PubMed
    1. J Biol Chem. 2012 Aug 31;287(36):30049-62 - PubMed
    1. Nature. 2009 May 21;459(7245):364-70 - PubMed
    1. Subcell Biochem. 2018;87:409-459 - PubMed
    1. Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11233-8 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

Feedback