Dimer dissociation is a key energetic event in the fold-switch pathway of KaiB

Simple item page
dc.contributor.authorRivera, Maira
dc.contributor.authorGalaz-Davison, Pablo
dc.contributor.authorRetamal-Farfan, Ignacio
dc.contributor.authorKomives, Elizabeth A.
dc.contributor.authorRamirez-Sarmiento, Cesar A.
dc.date.accessioned2025-01-20T21:10:46Z
dc.date.available2025-01-20T21:10:46Z
dc.date.issued2022
dc.description.abstractCyanobacteria possesses the simplest circadian clock, composed of three proteins that act as a phosphorylation oscillator: KaiA, KaiB, and KaiC. The timing of this oscillator is determined by the fold-switch of KaiB, a structural rearrangement of its C-terminal half that is accompanied by a change in the oligomerization state. During the day, KaiB forms a stable tetramer (gsKaiB), whereas it adopts a monomeric thioredoxin-like fold during the night (fsKaiB). Although the structures and functions of both native states are well studied, little is known about the sequence and structure determinants that control their structural interconversion. Here, we used confinement molecular dynamics (CCR-MD) and folding simulations using structure-based models to show that the dissociation of the gsKaiB dimer is a key energetic event for the fold-switch. Hydrogen-deuterium ex-change mass spectrometry (HDXMS) recapitulates the local stability of protein regions reported by CCR-MD, with both ap-proaches consistently indicating that the energy and backbone flexibility changes are solely associated with the region that fold-switches between gsKaiB and fsKaiB and that the localized regions that differentially stabilize gsKaiB also involve regions outside the dimer interface. Moreover, two mutants (R23C and R75C) previously reported to be relevant for altering the rhyth-micity of the Kai clock were also studied by HDXMS. Particularly, R75C populates dimeric and monomeric states with a deute-rium incorporation profile comparable to the one observed for fsKaiB, emphasizing the importance of the oligomerization state of KaiB for the fold-switch. These findings suggest that the information necessary to control the rhythmicity of the cyanobacterial biological clock is, to a great extent, encoded within the KaiB sequence.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bpj.2022.02.012
dc.identifier.eissn1542-0086
dc.identifier.issn0006-3495
dc.identifier.urihttps://doi.org/10.1016/j.bpj.2022.02.012
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93592
dc.identifier.wosidWOS:000772180600009
dc.issue.numero6
dc.language.isoen
dc.pagina.final955
dc.pagina.inicio943
dc.revistaBiophysical journal
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDimer dissociation is a key energetic event in the fold-switch pathway of KaiB
dc.typeartículo
dc.volumen121
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas