Quality control of protein complex assembly by a transmembrane recognition factor
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- dc.contributor.author Natarajan, Nivedita
- dc.contributor.author Foresti, Ombretta
- dc.contributor.author Wendrich, Kim
- dc.contributor.author Stein, Alexander
- dc.contributor.author Carvalho, Pedro C.
- dc.date.accessioned 2020-04-17T07:01:01Z
- dc.date.available 2020-04-17T07:01:01Z
- dc.date.issued 2020
- dc.description.abstract The inner nuclear membrane (INM) is continuous with the endoplasmic reticulum (ER) but harbors a distinctive proteome essential for nuclear functions. In yeast, the Asi1/Asi2/Asi3 ubiquitin ligase complex safeguards the INM proteome through the clearance of mislocalized ER membrane proteins. How the Asi complex selectively targets mislocalized proteins and coordinates its activity with other ER functions, such as protein biogenesis, is unclear. Here, we uncover a link between INM proteome identity and membrane protein complex assembly in the remaining ER. We show that lone proteins and complex subunits failing to assemble in the ER access the INM for Asi-mediated degradation. Substrates are recognized by direct binding of Asi2 to their transmembrane domains for subsequent ubiquitination by Asi1/Asi3 and membrane extraction. Our data suggest a model in which spatial segregation of membrane protein complex assembly and quality control improves assembly efficiency and reduces the levels of orphan subunits.
- dc.description.sponsorship N.N. was a recipient of an EMBO short-term fellowship. P.C. was supported by the Wellcome Trust. A.S. was supported by a European Research Council (ERC) grant under the Horizon2020 research and innovation program (grant 677770) and by the Deutsche Forschungsgemeinschaft (SFB1190, P15)
- dc.format.mimetype application/pdf
- dc.identifier.citation Natarajan N, Foresti O, Wendrich K, Stein A, Carvalho P. Quality control of protein complex assembly by a transmembrane recognition factor. Mol Cell. 2020 Jan 2; 77(1): 108-119.e9. DOI: 10.1016/j.molcel.2019.10.003
- dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2019.10.003
- dc.identifier.issn 1097-2765
- dc.identifier.uri http://hdl.handle.net/10230/44260
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Molecular Cell. 2020 Jan 2; 77(1): 108-19.e9
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/677770
- dc.rights © 2019 Nivedita Natarajan et al. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Proteïnes de membrana -- Metabolisme
- dc.subject.other Proteïnes fúngiques -- Metabolisme
- dc.title Quality control of protein complex assembly by a transmembrane recognition factor
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion