Structural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicase

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dc.citation.firstpage11965
dc.citation.issueNumber20
dc.citation.journalTitleNucleic Acids Research
dc.citation.lastpage11978
dc.citation.volumeNumber50
dc.contributor.authorLi, Zhuo
dc.contributor.authorKaur, Parminder
dc.contributor.authorLo, Chen-Yu
dc.contributor.authorChopra, Neil
dc.contributor.authorSmith, Jamie
dc.contributor.authorWang, Hong
dc.contributor.authorGao, Yang
dc.date.accessioned2023-01-27T14:47:28Z
dc.date.available2023-01-27T14:47:28Z
dc.date.issued2022
dc.description.abstractTwinkle is a mitochondrial replicative helicase which can self-load onto and unwind mitochondrial DNA. Nearly 60 mutations on Twinkle have been linked to human mitochondrial diseases. Using cryo-electron microscopy (cryo-EM) and high-speed atomic force microscopy (HS-AFM), we obtained the atomic-resolution structure of a vertebrate Twinkle homolog with DNA and captured in real-time how Twinkle is self-loaded onto DNA. Our data highlight the important role of the non-catalytic N-terminal domain of Twinkle. The N-terminal domain directly contacts the C-terminal helicase domain, and the contact interface is a hotspot for disease-related mutations. Mutations at the interface destabilize Twinkle hexamer and reduce helicase activity. With HS-AFM, we observed that a highly dynamic Twinkle domain, which is likely to be the N-terminal domain, can protrude ∼5 nm to transiently capture nearby DNA and initialize Twinkle loading onto DNA. Moreover, structural analysis and subunit doping experiments suggest that Twinkle hydrolyzes ATP stochastically, which is distinct from related helicases from bacteriophages.
dc.identifier.citationLi, Zhuo, Kaur, Parminder, Lo, Chen-Yu, et al.. "Structural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicase." <i>Nucleic Acids Research,</i> 50, no. 20 (2022) Oxford University Press: 11965-11978. https://doi.org/10.1093/nar/gkac1089.
dc.identifier.digitalgkac1089
dc.identifier.doihttps://doi.org/10.1093/nar/gkac1089
dc.identifier.urihttps://hdl.handle.net/1911/114278
dc.language.isoeng
dc.publisherOxford University Press
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleStructural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicase
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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