Concerted transformation of a hyper-paused transcription complex and its reinforcing protein

dc.contributor.authorZuber, Philipp K.
dc.contributor.authorSaid, Nelly
dc.contributor.authorHilal, Tarek
dc.contributor.authorWang, Bing
dc.contributor.authorLoll, Bernhard
dc.contributor.authorGonzalez-Higueras, Jorge
dc.contributor.authorRamirez-Sarmiento, Cesar A.
dc.contributor.authorBelogurov, Georgiy A.
dc.contributor.authorArtsimovitch, Irina
dc.contributor.authorWahl, Markus C.
dc.contributor.authorKnauer, Stefan H.
dc.date.accessioned2025-01-20T16:14:34Z
dc.date.available2025-01-20T16:14:34Z
dc.date.issued2024
dc.description.abstractRfaH, a paralog of the universally conserved NusG, binds to RNA polymerases (RNAP) and ribosomes to activate expression of virulence genes. In free, autoinhibited RfaH, an alpha-helical KOW domain sequesters the RNAP-binding site. Upon recruitment to RNAP paused at an ops site, KOW is released and refolds into a beta-barrel, which binds the ribosome. Here, we report structures of ops-paused transcription elongation complexes alone and bound to the autoinhibited and activated RfaH, which reveal swiveled, pre-translocated pause states stabilized by an ops hairpin in the non-template DNA. Autoinhibited RfaH binds and twists the ops hairpin, expanding the RNA:DNA hybrid to 11 base pairs and triggering the KOW release. Once activated, RfaH hyper-stabilizes the pause, which thus requires anti-backtracking factors for escape. Our results suggest that the entire RfaH cycle is solely determined by the ops and RfaH sequences and provide insights into mechanisms of recruitment and metamorphosis of NusG homologs across all life.
dc.description.abstractHere, authors use cryoEM, biochemistry and molecular dynamics simulations to delineate a functional cycle of RfaH, a universally conserved transcription factor that undergoes a fold-switch during recruitment to the transcribing RNA polymerase.
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41467-024-47368-4
dc.identifier.eissn2041-1723
dc.identifier.urihttps://doi.org/10.1038/s41467-024-47368-4
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/90448
dc.identifier.wosidWOS:001198902100015
dc.issue.numero1
dc.language.isoen
dc.revistaNature communications
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleConcerted transformation of a hyper-paused transcription complex and its reinforcing protein
dc.typeartículo
dc.volumen15
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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