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dc.contributor.authorChiarini, Valerio
dc.contributor.authorTossavainen, Helena
dc.contributor.authorSharma, Vivek
dc.contributor.authorColotti, Gianni
dc.date.accessioned2019-10-07T11:57:06Z
dc.date.available2019-10-07T11:57:06Z
dc.date.issued2019
dc.identifier.citationChiarini, V., Tossavainen, H., Sharma, V., & Colotti, G. (2019). NMR structure of a non-conjugatable, ADP-ribosylation associated, ubiquitin-like domain from Tetrahymena thermophila polyubiquitin locus. <i>Biochimica et Biophysica Acta : General Subjects</i>, <i>1863</i>(4), 749-759. <a href="https://doi.org/10.1016/j.bbagen.2019.01.014" target="_blank">https://doi.org/10.1016/j.bbagen.2019.01.014</a>
dc.identifier.otherCONVID_33123122
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/65762
dc.description.abstractBackground. Ubiquitin-like domains (UbLs), in addition to being post-translationally conjugated to the target through the E1-E2-E3 enzymatic cascade, can be translated as a part of the protein they ought to regulate. As integral UbLs coexist with the rest of the protein, their structural properties can differ from canonical ubiquitin, depending on the protein context and how they interact with it. In this work, we investigate T.th-ubl5, a UbL present in a polyubiquitin locus of Tetrahymena thermophila, which is integral to an ADP-ribosyl transferase protein. Only one other co-occurrence of these two domains within the same protein has been reported. Methods. NMR, multiple sequence alignment, MD simulations and SPR have been used to characterize the structure of T.th-ubl5, identify putative binders and experimentally test the interaction, respectively. Results. Molecular dynamics simulations showed that T.th-ubl5 is unable to bind the proteasome like ubiquitin due to the lack of the conserved hydrophobic patch. Of other integral UbLs identified by structural and sequence alignment, T.th-ubl5 showed high structural and sequence resemblance with the Ras-binding epitope of FERM UbLs. SPR experiments confirmed that a strong and specific interaction occurs between T.th-ubl5 and T.th-Ras. Conclusion. Data indicate that T.th-ubl5 does not interact with the proteasome like ubiquitin but acts as a decoy for the recruitment of Ras protein by the ADP-ribosyl transferase domain. General significance. Mono-ADP-ribosylation of Ras proteins is known as a prerogative of bacterial toxins. T.th-ubl5 mediated recruitment of Ras highlights the possibility of an unprecedented post-translational modification with interesting implication for signalling pathways.en
dc.format.mimetypeapplication/pdf
dc.languageeng
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofseriesBiochimica et Biophysica Acta : General Subjects
dc.rightsCC BY 4.0
dc.subject.otherUbiquitin-like domains
dc.subject.otherstructure-function relationship
dc.subject.otherpost-translational modification
dc.subject.otherprotein-protein interaction
dc.subject.otherNMR spectroscopy
dc.subject.othermolecular dynamics simulations
dc.titleNMR structure of a non-conjugatable, ADP-ribosylation associated, ubiquitin-like domain from Tetrahymena thermophila polyubiquitin locus
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201910074344
dc.contributor.laitosKemian laitosfi
dc.contributor.laitosDepartment of Chemistryen
dc.contributor.oppiaineNanoscience Centerfi
dc.contributor.oppiaineNanoscience Centeren
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.description.reviewstatuspeerReviewed
dc.format.pagerange749-759
dc.relation.issn0304-4165
dc.relation.numberinseries4
dc.relation.volume1863
dc.type.versionpublishedVersion
dc.rights.copyright© 2019 The Authors
dc.rights.accesslevelopenAccessfi
dc.subject.ysomolekyylidynamiikka
dc.subject.ysospektroskopia
dc.subject.ysoNMR-spektroskopia
dc.subject.ysoproteiinit
dc.subject.ysoubikitiinit
dc.format.contentfulltext
jyx.subject.urihttp://www.yso.fi/onto/yso/p29332
jyx.subject.urihttp://www.yso.fi/onto/yso/p10176
jyx.subject.urihttp://www.yso.fi/onto/yso/p26254
jyx.subject.urihttp://www.yso.fi/onto/yso/p4332
jyx.subject.urihttp://www.yso.fi/onto/yso/p27556
dc.rights.urlhttps://creativecommons.org/licenses/by/4.0/
dc.relation.doi10.1016/j.bbagen.2019.01.014
jyx.fundinginformationThis work was supported by the Integrative Life Science Doctoral Program (ILS). VS acknowledges funding from the Academy of Finland, University of Helsinki, Sigrid Jusélius Foundation and the Magnus Ehrnrooth Foundation. CSC-IT Center for Science, Finland, is acknowledged for computational resources. The authors wish to thank Dr. Joseph Harrison for providing the updated list of ubiquitin-like domains present in UbSRD database. We acknowledge “Quality methods for Design of Experiments in Scientific Research”, in the FaReBio di Qualità Project; the Flagship Project Nanomax: “NADINE: Nanotechnology-based Diagnostics In Neurological diseases and Experimental oncology”; PRIN 20154JRJPP MIUR; Progetto Ricerca Finalizzata Min. Salute RF-2016-02364123 RAREST-JHD to G.C.


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