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

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dc.citation.firstpage11965en_US
dc.citation.issueNumber20en_US
dc.citation.journalTitleNucleic Acids Researchen_US
dc.citation.lastpage11978en_US
dc.citation.volumeNumber50en_US
dc.contributor.authorLi, Zhuoen_US
dc.contributor.authorKaur, Parminderen_US
dc.contributor.authorLo, Chen-Yuen_US
dc.contributor.authorChopra, Neilen_US
dc.contributor.authorSmith, Jamieen_US
dc.contributor.authorWang, Hongen_US
dc.contributor.authorGao, Yangen_US
dc.date.accessioned2023-01-27T14:47:28Zen_US
dc.date.available2023-01-27T14:47:28Zen_US
dc.date.issued2022en_US
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.en_US
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.en_US
dc.identifier.digitalgkac1089en_US
dc.identifier.doihttps://doi.org/10.1093/nar/gkac1089en_US
dc.identifier.urihttps://hdl.handle.net/1911/114278en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
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.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleStructural and dynamic basis of DNA capture and translocation by mitochondrial Twinkle helicaseen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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