K48- and K63-linked ubiquitin chain interactome reveals branch- and chain length-specific ubiquitin interactors

  • The ubiquitin (Ub) code denotes the complex Ub architectures, including Ub chains of different length, linkage-type and linkage combinations, which enable ubiquitination to control a wide range of protein fates. Although many linkage-specific interactors have been described, how interactors are able to decode more complex architectures is not fully understood. We conducted a Ub interactor screen, in humans and yeast, using Ub chains of varying length, as well as, homotypic and heterotypic branched chains of the two most abundant linkage types – K48- and K63-linked Ub. We identified some of the first K48/K63 branch-specific Ub interactors, including histone ADP-ribosyltransferase PARP10/ARTD10, E3 ligase UBR4 and huntingtin-interacting protein HIP1. Furthermore, we revealed the importance of chain length by identifying interactors with a preference for Ub3 over Ub2 chains, including Ub-directed endoprotease DDI2, autophagy receptor CCDC50 and p97-adaptor FAF1. Crucially, we compared datasets collected using two common DUB inhibitors – Chloroacetamide and N-ethylmaleimide. This revealed inhibitor-dependent interactors, highlighting the importance of inhibitor consideration during pulldown studies. This dataset is a key resource for understanding how the Ub code is read.

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Metadaten
Author:Anita WalthoORCiD, Oliver PoppORCiD, Christopher LenzORCiD, Lukas PluskaORCiDGND, Volker DötschORCiDGND, Phillip MertinsORCiD, Thomas SommerORCiDGND
URN:urn:nbn:de:hebis:30:3-830323
URL:https://www.biorxiv.org/content/10.1101/2024.01.08.574586v1
DOI:https://doi.org/10.1101/2024.01.08.574586
Parent Title (English):bioRxiv
Publisher:bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2024/01/08
Date of first Publication:2024/01/08
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/03/07
Issue:2024.01.08.574586 Version 1
Edition:Version 1
Page Number:43
HeBIS-PPN:51688929X
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:0 Informatik, Informationswissenschaft, allgemeine Werke / 00 Informatik, Wissen, Systeme / 004 Datenverarbeitung; Informatik
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International