7ZJ3

Structure of TRIM2 RING domain in complex with UBE2D1~Ub conjugate

Summary for 7ZJ3

• Entry DOI: 10.2210/pdb7zj3/pdb
• Descriptor: Tripartite motif-containing protein 2, Ubiquitin-conjugating enzyme E2 D1, Polyubiquitin-C, ... (5 entities in total)
• Functional Keywords: ubiquitin ligase, trim protein, ring ligase, ligase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 146643.29

Authors

Esposito, D.,Garza-Garcia, A.,Dudley-Fraser, J.,Rittinger, K. (deposition date: 2022-04-08, release date: 2022-11-30, Last modification date: 2024-01-31)

Primary citation

Esposito, D.,Dudley-Fraser, J.,Garza-Garcia, A.,Rittinger, K.
Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity.
Nat Commun, 13:7583-7583, 2022

PubMed Abstract: Tripartite motif (TRIM) proteins constitute a large family of RING-type E3 ligases that share a conserved domain architecture. TRIM2 and TRIM3 are paralogous class VII TRIM members that are expressed mainly in the brain and regulate different neuronal functions. Here we present a detailed structure-function analysis of TRIM2 and TRIM3, which despite high sequence identity, exhibit markedly different self-association and activity profiles. We show that the isolated RING domain of human TRIM3 is monomeric and inactive, and that this lack of activity is due to a few placental mammal-specific amino acid changes adjacent to the core RING domain that prevent self-association but not E2 recognition. We demonstrate that the activity of human TRIM3 RING can be restored by substitution with the relevant region of human TRIM2 or by hetero-dimerization with human TRIM2, establishing that subtle amino acid changes can profoundly affect TRIM protein activity. Finally, we show that TRIM2 and TRIM3 interact in a cellular context via their filamin and coiled-coil domains, respectively.

PubMed: 36481767
DOI: 10.1038/s41467-022-35300-7

Experimental method

X-RAY DIFFRACTION (2.53 Å)