The structural assembly switch of cell division protein FtsZ probed with fluorescent allosteric inhibitors

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dc.contributor.authorArtola Pérez de Azanza, Marta Elena
dc.contributor.authorRuiz Ávila, Laura, Laura B.
dc.contributor.authorRamírez Aportela, Erney
dc.contributor.authorFernando Martínez, R.
dc.contributor.authorAraujo Bazán, Lidia
dc.contributor.authorVázquez Villa, Henar
dc.contributor.authorMartín Fontecha, María del Mar
dc.contributor.authorOliva Blanco, María Ángela
dc.contributor.authorMartín Galiano, Antonio Javier
dc.contributor.authorChacón Montes, Pablo
dc.contributor.authorLópez Rodríguez, María Luz
dc.contributor.authorAndreu Rodríguez, José Manuel
dc.contributor.authorHuecas Gayo, Sonia
dc.date.accessioned2023-06-17T22:15:56Z
dc.date.available2023-06-17T22:15:56Z
dc.date.issued2017
dc.descriptionThe article was received on 24 Aug 2016, accepted on 19 Oct 2016 and first published on 21 Oct 2016
dc.description.abstractFtsZ is a widely conserved tubulin-like GTPase that directs bacterial cell division and a new target for antibiotic discovery. This protein assembly machine cooperatively polymerizes forming single-stranded filaments, by means of self-switching between inactive and actively associating monomer conformations. The structural switch mechanism was proposed to involve a movement of the C-terminal and N-terminal FtsZ domains, opening a cleft between them, allosterically coupled to the formation of a tight association interface between consecutive subunits along the filament. The effective antibacterial benzamide PC190723 binds into the open interdomain cleft and stabilizes FtsZ filaments, thus impairing correct formation of the FtsZ ring for cell division. We have designed fluorescent analogs of PC190723 to probe the FtsZ structural assembly switch. Among them, nitrobenzoxadiazole probes specifically bind to assembled FtsZ rather than to monomers. Probes with several spacer lengths between the fluorophore and benzamide moieties suggest a binding site extension along the interdomain cleft. These probes label FtsZ rings of live Bacillus subtilis and Staphylococcus aureus, without apparently modifying normal cell morphology and growth, but at high concentrations they induce impaired bacterial division phenotypes typical of benzamide antibacterials. During the FtsZ assembly-disassembly process, the fluorescence anisotropy of the probes changes upon binding and dissociating from FtsZ, thus reporting open and closed FtsZ interdomain clefts. Our results demonstrate the structural mechanism of the FtsZ assembly switch, and suggest that the probes bind into the open clefts in cellular FtsZ polymers preferably to unassembled FtsZ in the bacterial cytosol.
dc.description.departmentSección Deptal. de Química Orgánica (Óptica y Optometría)
dc.description.facultyFac. de Óptica y Optometría
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía y Competitividad de España (MINECO)
dc.description.sponsorshipCSIC
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/45852
dc.identifier.doi10.1039/C6SC03792E
dc.identifier.issn2041-6520
dc.identifier.officialurlhttp://dx.doi.org/10.1039/C6SC03792E
dc.identifier.relatedurlhttp://pubs.rsc.org/en/content/articlelanding/2017/sc/c6sc03792e#!divAbstract
dc.identifier.relatedurlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460597/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/18293
dc.issue.number8
dc.journal.titleChemical Science
dc.language.isoeng
dc.page.final1534
dc.page.initial1525
dc.publisherRSC
dc.relation.projectIDBFU2014-51823-R
dc.relation.projectIDBFU2013-44308-P
dc.relation.projectIDSAF2013-48271-C2
dc.relation.projectIDCM S2010/BMD-2353
dc.relation.projectIDRamon y Cajal 2011-07900
dc.relation.projectIDFPDI-2013-16470
dc.rightsAtribución-NoComercial 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/es/
dc.subject.cdu547
dc.subject.cdu543.426
dc.subject.cdu577.18.08
dc.subject.keywordProtein
dc.subject.keywordCell division
dc.subject.keywordFtsZ
dc.subject.keywordFluorescence
dc.subject.keywordPolymers
dc.subject.keywordBacterial cell division
dc.subject.ucmBiología celular (Biología)
dc.subject.ucmQuímica orgánica (Farmacia)
dc.subject.unesco2407 Biología Celular
dc.titleThe structural assembly switch of cell division protein FtsZ probed with fluorescent allosteric inhibitors
dc.typejournal article
dspace.entity.typePublication
relation.isAuthorOfPublication3ff71f46-a523-4f60-95a6-c6faed83d4cf
relation.isAuthorOfPublicationcefbe1ad-058c-44c1-9abd-46a7755783a7
relation.isAuthorOfPublication.latestForDiscovery3ff71f46-a523-4f60-95a6-c6faed83d4cf
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