| Literature DB >> 29547724 |
Tales Rocha de Moura1, Sina Mozaffari-Jovin2, Csaba Zoltán Kibédi Szabó1, Jana Schmitzová1, Olexandr Dybkov3, Constantin Cretu1, Michael Kachala4, Dmitri Svergun5, Henning Urlaub6, Reinhard Lührmann3, Vladimir Pena7.
Abstract
Human nineteen complex (NTC) acts as a multimeric E3 ubiquitin ligase in DNA repair and splicing. The transfer of ubiquitin is mediated by Prp19-a homotetrameric component of NTC whose elongated coiled coils serve as an assembly axis for two other proteins called SPF27 and CDC5L. We find that Prp19 is inactive on its own and have elucidated the structural basis of its autoinhibition by crystallography and mutational analysis. Formation of the NTC core by stepwise assembly of SPF27, CDC5L, and PLRG1 onto the Prp19 tetramer enables ubiquitin ligation. Protein-protein crosslinking of NTC, functional assays in vitro, and assessment of its role in DNA damage response provide mechanistic insight into the organization of the NTC core and the communication between PLRG1 and Prp19 that enables E3 activity. This reveals a unique mode of regulation for a complex E3 ligase and advances understanding of its dynamics in various cellular pathways.Entities:
Keywords: DNA damage response; E3 ubiquitin ligase; Prp19/NTC complex; pre-mRNA splicing
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Year: 2018 PMID： 29547724 DOI： 10.1016/j.molcel.2018.02.022
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970