Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity
journal contributionposted on 2020-08-12, 13:43 authored by Marios G Koliopoulos, Diego Esposito, Evangelos Christodoulou, Ian A Taylor, Katrin Rittinger
TRIM E3 ubiquitin ligases regulate a wide variety of cellular processes and are particularly important during innate immune signalling events. They are characterized by a conserved tripartite motif in their N-terminal portion which comprises a canonical RING domain, one or two B-box domains and a coiled-coil region that mediates ligase dimerization. Self-association via the coiled-coil has been suggested to be crucial for catalytic activity of TRIMs; however, the precise molecular mechanism underlying this observation remains elusive. Here, we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and an ubiquitin-loaded E2 identifies the structural and mechanistic features that promote a closed E2~Ub conformation to activate the thioester for ubiquitin transfer allowing us to propose a model for the regulation of activity in the full-length protein. Our data reveal an unexpected diversity in the self-association mechanism of TRIMs that might be crucial for their biological function.
TRIM25TRIM32enzyme mechanismprotein structureubiquitin ligaseCrystallizationHumansProtein ConformationProtein MultimerizationTranscription FactorsTripartite Motif ProteinsUbiquitin-Protein LigasesUbiquitinationRittinger FC001142Taylor, I FC001178SBNMR-ackDevelopmental Biology06 Biological Sciences08 Information and Computing Sciences11 Medical and Health Sciences