7BBD

Crystal structure of monoubiquitinated TRIM21 RING (Ub-RING) In complex with ubiquitin charged Ube2N (Ube2N~Ub) and Ube2V2

Summary for 7BBD

• Entry DOI: 10.2210/pdb7bbd/pdb
• Descriptor: Polyubiquitin-B,E3 ubiquitin-protein ligase TRIM21, Polyubiquitin-C, Ubiquitin-conjugating enzyme E2 variant 2, ... (6 entities in total)
• Functional Keywords: e3 ubiquitin ligase, e2 conjugating enzyme, ubiquitin chain elongation, ligase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 61198.92

Authors

Kiss, L.,Neuhaus, D.,James, L.C. (deposition date: 2020-12-17, release date: 2021-01-27, Last modification date: 2024-01-31)

Primary citation

Kiss, L.,Clift, D.,Renner, N.,Neuhaus, D.,James, L.C.
RING domains act as both substrate and enzyme in a catalytic arrangement to drive self-anchored ubiquitination.
Nat Commun, 12:1220-1220, 2021

PubMed Abstract: Attachment of ubiquitin (Ub) to proteins is one of the most abundant and versatile of all posttranslational modifications and affects outcomes in essentially all physiological processes. RING E3 ligases target E2 Ub-conjugating enzymes to the substrate, resulting in its ubiquitination. However, the mechanism by which a ubiquitin chain is formed on the substrate remains elusive. Here we demonstrate how substrate binding can induce a specific RING topology that enables self-ubiquitination. By analyzing a catalytically trapped structure showing the initiation of TRIM21 RING-anchored ubiquitin chain elongation, and in combination with a kinetic study, we illuminate the chemical mechanism of ubiquitin conjugation. Moreover, biochemical and cellular experiments show that the topology found in the structure can be induced by substrate binding. Our results provide insights into ubiquitin chain formation on a structural, biochemical and cellular level with broad implications for targeted protein degradation.

PubMed: 33619271
DOI: 10.1038/s41467-021-21443-6

Experimental method

X-RAY DIFFRACTION (2.2 Å)