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Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity

DOI: 10.15252/embj.201593741 DOI Help

Authors: Marios Koliopoulos (The Francis Crick Institute) , Diego Esposito (The Francis Crick Institute) , Evangelos Christodoulou (The Francis Crick Institute) , Ian Taylor (The Francis Crick Institute) , Katrin Rittinger (The Francis Crick Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Embo Journal , VOL 35 , PAGES 1204 - 1218

State: Published (Approved)
Published: May 2016
Diamond Proposal Number(s): 9826

Open Access Open Access

Abstract: 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.

Journal Keywords: enzyme mechanism; protein structure; TRIM25; TRIM32; ubiquitin ligase

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: B21-High Throughput SAXS

Other Facilities: SWING beamline at SOLEIL, ESRF Synchrotron Radiation Facility (Grenoble, France)

Added On: 12/07/2016 15:44

The EMBO Journal - 2016 - Koliopoulos - Functional role of TRIM E3 ligase oligomerization and regulation of catalytic.pdf

Discipline Tags:

Biochemistry Chemistry Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)