EMD-17801

Single-particle
6.88 Å
EMD-17801 Deposition: 07/07/2023
Map released: 14/02/2024
Last modified: 28/02/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-17801

NEDD8-CUL2-RBX1-ELOB/C-FEM1C-SIL1 conformation 2

EMD-17801

Single-particle
6.88 Å
EMD-17801 Deposition: 07/07/2023
Map released: 14/02/2024
Last modified: 28/02/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: NEDD8-CUL2-RBX1-ELOB/C-FEM1C-SIL1 conformation 2

Deposition Authors: Liwocha J , Prabu JR , Kleiger G , Schulman BA
Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases.
Liwocha J , Li J , Purser N, Rattanasopa C, Maiwald S , Krist DT, Scott DC, Steigenberger B, Prabu JR , Schulman BA , Kleiger G
(2024) Nat Struct Mol Biol , 31 , 378 - 389
PUBMED: 38326650
DOI: doi:10.1038/s41594-023-01206-1
ISSN: 1545-9985
Abstract:
E3 ubiquitin ligases, in collaboration with E2 ubiquitin-conjugating enzymes, modify proteins with poly-ubiquitin chains. Cullin-RING ligase (CRL) E3s use Cdc34/UBE2R-family E2s to build Lys48-linked poly-ubiquitin chains to control an enormous swath of eukaryotic biology. Yet the molecular mechanisms underlying this exceptional linkage specificity and millisecond kinetics of poly-ubiquitylation remain unclear. Here we obtain cryogenic-electron microscopy (cryo-EM) structures that provide pertinent insight into how such poly-ubiquitin chains are forged. The CRL RING domain not only activates the E2-bound ubiquitin but also shapes the conformation of a distinctive UBE2R2 loop, positioning both the ubiquitin to be transferred and the substrate-linked acceptor ubiquitin within the active site. The structures also reveal how the ubiquitin-like protein NEDD8 uniquely activates CRLs during chain formation. NEDD8 releases the RING domain from the CRL, but unlike previous CRL-E2 structures, does not contact UBE2R2. These findings suggest how poly-ubiquitylation may be accomplished by many E2s and E3s.