Cryo-EM reveals distinct conformations of ATP synthase on exposure to ATP.

TitleCryo-EM reveals distinct conformations of ATP synthase on exposure to ATP.
Publication TypeJournal Article
Year of Publication2019
AuthorsSobti, M, Ishmukhametov, R, Bouwer, JC, Ayer, A, Suarna, C, Smith, NJ, Christie, M, Stocker, R, Duncan, TM, Stewart, AG
Date Published2019 Mar 26

ATP synthase produces the majority of cellular energy in most cells. We have previously reported cryo-EM maps of autoinhibited ATP synthase imaged without addition of nucleotide (Sobti et al. 2016), indicating that the subunit ε engages the α, β and γ subunits to lock the enzyme and prevent functional rotation. Here we present multiple cryo-EM reconstructions of the enzyme frozen after the addition of MgATP to identify the changes that occur when this ε inhibition is removed. The maps generated show that, after exposure to MgATP, ATP synthase adopts a different conformation with a catalytic subunit changing conformation substantially and the ε C-terminal domain transitioning via an intermediate 'half-up' state to a condensed 'down' state. This work provides direct evidence for unique conformational states that occur in ATP synthase when ATP binding prevents the ε C-terminal domain from entering the inhibitory 'up' state.

Alternate JournalElife
Citation Key10.7554/eLife.43864
PubMed ID30912741
PubMed Central IDPMC6449082
Grant ListAPP1146403 / / National Health and Medical Research Council /
BB/L01985X/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
DE160100608 / / Australian Research Council /
APP1159347 / / National Health and Medical Research Council /
Future Leader Fellowship / / National Heart Foundation of Australia /