Show simple item record

dc.contributor.authorMontgomery, Martin G
dc.contributor.authorPetri, Jessica
dc.contributor.authorSpikes, Tobias E
dc.contributor.authorWalker, John
dc.date.accessioned2022-01-07T00:31:39Z
dc.date.available2022-01-07T00:31:39Z
dc.date.issued2021-11-23
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332260
dc.description.abstractThe structure has been determined by electron cryomicroscopy of the adenosine triphosphate (ATP) synthase from Mycobacterium smegmatis This analysis confirms features in a prior description of the structure of the enzyme, but it also describes other highly significant attributes not recognized before that are crucial for understanding the mechanism and regulation of the mycobacterial enzyme. First, we resolved not only the three main states in the catalytic cycle described before but also eight substates that portray structural and mechanistic changes occurring during a 360° catalytic cycle. Second, a mechanism of auto-inhibition of ATP hydrolysis involves not only the engagement of the C-terminal region of an α-subunit in a loop in the γ-subunit, as proposed before, but also a "fail-safe" mechanism involving the b'-subunit in the peripheral stalk that enhances engagement. A third unreported characteristic is that the fused bδ-subunit contains a duplicated domain in its N-terminal region where the two copies of the domain participate in similar modes of attachment of the two of three N-terminal regions of the α-subunits. The auto-inhibitory plus the associated "fail-safe" mechanisms and the modes of attachment of the α-subunits provide targets for development of innovative antitubercular drugs. The structure also provides support for an observation made in the bovine ATP synthase that the transmembrane proton-motive force that provides the energy to drive the rotary mechanism is delivered directly and tangentially to the rotor via a Grotthuss water chain in a polar L-shaped tunnel.
dc.format.mediumPrint
dc.publisherProceedings of the National Academy of Sciences
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectATP synthase
dc.subjectmycobacteria
dc.subjectregulation
dc.subjectrotary mechanism
dc.subjectstructure
dc.subjectAdenosine Triphosphate
dc.subjectAnimals
dc.subjectAntitubercular Agents
dc.subjectBacterial Proteins
dc.subjectCattle
dc.subjectCryoelectron Microscopy
dc.subjectHydrolysis
dc.subjectMitochondrial Proton-Translocating ATPases
dc.subjectModels, Molecular
dc.subjectMycobacterium smegmatis
dc.subjectProtein Conformation
dc.subjectProtein Subunits
dc.subjectProteins
dc.subjectProton-Motive Force
dc.subjectTuberculosis
dc.titleStructure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis.
dc.typeArticle
dc.publisher.departmentMrc Mitochondrial Biology Unit
dc.date.updated2022-01-06T11:16:30Z
prism.endingPagee2111899118
prism.issueIdentifier47
prism.numberARTN e2111899118
prism.publicationDate2021
prism.publicationNameProc Natl Acad Sci U S A
prism.startingPagee2111899118
prism.volume118
dc.identifier.doi10.17863/CAM.79705
dcterms.dateAccepted2021-10-13
rioxxterms.versionofrecord10.1073/pnas.2111899118
rioxxterms.versionVoR
dc.contributor.orcidMontgomery, Martin G [0000-0001-6142-9423]
dc.contributor.orcidSpikes, Tobias E [0000-0002-2432-8006]
dc.contributor.orcidWalker, John [0000-0001-7929-2162]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_EX_MR/M009858/1)
pubs.funder-project-idMRC (MC_UU_00015/8)
cam.issuedOnline2021-11-15
cam.depositDate2022-01-06
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International