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dc.contributor.authorBason, John V
dc.contributor.authorMontgomery, Martin G
dc.contributor.authorLeslie, Andrew GW
dc.contributor.authorWalker, John E
dc.date.accessioned2018-11-13T00:31:11Z
dc.date.available2018-11-13T00:31:11Z
dc.date.issued2015-05-12
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284978
dc.description.abstractThe rotation of the central stalk of F1-ATPase is driven by energy derived from the sequential binding of an ATP molecule to its three catalytic sites and the release of the products of hydrolysis. In human F1-ATPase, each 360° rotation consists of three 120° steps composed of substeps of about 65°, 25°, and 30°, with intervening ATP binding, phosphate release, and catalytic dwells, respectively. The F1-ATPase inhibitor protein, IF1, halts the rotary cycle at the catalytic dwell. The human and bovine enzymes are essentially identical, and the structure of bovine F1-ATPase inhibited by IF1 represents the catalytic dwell state. Another structure, described here, of bovine F1-ATPase inhibited by an ATP analog and the phosphate analog, thiophosphate, represents the phosphate binding dwell. Thiophosphate is bound to a site in the α(E)β(E)-catalytic interface, whereas in F1-ATPase inhibited with IF1, the equivalent site is changed subtly and the enzyme is incapable of binding thiophosphate. These two structures provide a molecular mechanism of how phosphate release generates a rotary substep as follows. In the active enzyme, phosphate release from the β(E)-subunit is accompanied by a rearrangement of the structure of its binding site that prevents released phosphate from rebinding. The associated extrusion of a loop in the β(E)-subunit disrupts interactions in the α(E)β(E-)catalytic interface and opens it to its fullest extent. Other rearrangements disrupt interactions between the γ-subunit and the C-terminal domain of the α(E)-subunit. To restore most of these interactions, and to make compensatory new ones, the γ-subunit rotates through 25°-30°.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherProceedings of the National Academy of Sciences
dc.rightsPublisher's own licence
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectCattle
dc.subjectHumans
dc.subjectPhosphates
dc.subjectProton-Translocating ATPases
dc.subjectAdenosine Diphosphate
dc.subjectCrystallography, X-Ray
dc.subjectTemperature
dc.subjectCatalytic Domain
dc.subjectProtein Structure, Secondary
dc.subjectProtein Binding
dc.subjectHydrolysis
dc.subjectModels, Molecular
dc.subjectMolecular Motor Proteins
dc.titleHow release of phosphate from mammalian F1-ATPase generates a rotary substep.
dc.typeArticle
prism.endingPage6014
prism.issueIdentifier19
prism.publicationDate2015
prism.publicationNameProc Natl Acad Sci U S A
prism.startingPage6009
prism.volume112
dc.identifier.doi10.17863/CAM.32349
rioxxterms.versionofrecord10.1073/pnas.1506465112
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2015-05
dc.contributor.orcidMontgomery, Martin [0000-0001-6142-9423]
dc.contributor.orcidWalker, John [0000-0001-7929-2162]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_U105663150)
cam.issuedOnline2015-04-27


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