{"doi":"10.3389/fmicb.2022.965620","title":"F1FO ATP synthase molecular motor mechanisms","abstract":"The F-ATP synthase, consisting of F 1 and F O motors connected by a central rotor and the stators, is the enzyme responsible for synthesizing the majority of ATP in all organisms. The F 1 (αβ) 3 ring stator contains three catalytic sites. Single-molecule F 1 rotation studies revealed that ATP hydrolysis at each catalytic site (0°) precedes a power-stroke that rotates subunit-γ 120° with angular velocities that vary with rotational position. Catalytic site conformations vary relative to subunit-γ position (β E , empty; β D , ADP bound; β T , ATP-bound). During a power stroke, β E binds ATP (0°–60°) and β D releases ADP (60°–120°). Årrhenius analysis of the power stroke revealed that elastic energy powers rotation via unwinding the γ-subunit coiled-coil. Energy from ATP binding at 34° closes β E upon subunit-γ to drive rotation to 120° and forcing the subunit-γ to exchange its tether from β E to β D , which changes catalytic site conformations. In F 1 F O , the membrane-bound F O complex contains a ring of c-subunits that is attached to subunit-γ. This c-ring rotates relative to the subunit-a stator in response to transmembrane proton flow driven by a pH gradient, which drives subunit-γ rotation in the opposite direction to force ATP synthesis in F 1 . Single-molecule studies of F 1 F O embedded in lipid bilayer nanodisks showed that the c-ring transiently stopped F 1 -ATPase-driven rotation every 36° (at each c-subunit in the c 10 -ring of E. coli F 1 F O ) and was able to rotate 11° in the direction of ATP synthesis. Protonation and deprotonation of the conserved carboxyl group on each c-subunit is facilitated by separate groups of subunit-a residues, which were determined to have different pKa’s. Mutations of any of any residue from either group changed both pKa values, which changed the occurrence of the 11° rotation proportionately. This supports a Grotthuss mechanism for proton translocation and indicates that proton translocation occurs during the 11° steps. This is consistent with a mechanism in which each 36° of rotation the c-ring during ATP synthesis involves a proton translocation-dependent 11° rotation of the c-ring, followed by a 25° rotation driven by electrostatic interaction of the negatively charged unprotonated carboxyl group to the positively charged essential arginine in subunit-a.","journal":"Frontiers in Microbiology","year":2022,"id":241303,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":870646,"name":"Zain A. Bukhari","orcid":null,"position":1,"is_corresponding":false},{"id":820942,"name":"Seiga Yanagisawa","orcid":null,"position":2,"is_corresponding":false},{"id":820472,"name":"Wayne D. Frasch","orcid":"0000-0001-6590-7437","position":0,"is_corresponding":true}],"reference_count":133,"raw_metadata":null,"created_at":"2026-07-19T00:22:56.227656Z","pmid":"36081786","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}