9LGS

R-degron fused ZZ-domain of the Arabidopsis thaliana E3 ubiquitin-protein ligase BIG

Summary for 9LGS

• Entry DOI: 10.2210/pdb9lgs/pdb
• Descriptor: Auxin transport protein BIG, ZINC ION, NICKEL (II) ION, ... (4 entities in total)
• Functional Keywords: complex, zz-domain, arabidopsis thaliana, big, e3-ubiquitin ligase, ligase
• Biological source: Arabidopsis thaliana (thale cress)
• Total number of polymer chains: 3
• Total formula weight: 20877.91

Authors

Yang, W.S.,Lee, J.,Song, H.K. (deposition date: 2025-01-10, release date: 2025-09-17)

Primary citation

Grabarczyk, D.B.,Ehrmann, J.F.,Murphy, P.,Yang, W.S.,Kurzbauer, R.,Bell, L.E.,Deszcz, L.,Neuhold, J.,Schleiffer, A.,Shulkina, A.,Lee, J.,Shin, J.S.,Meinhart, A.,Versteeg, G.A.,Zavodszky, E.,Song, H.K.,Hegde, R.S.,Clausen, T.
Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.
Science, 389:909-914, 2025

PubMed Abstract: Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as an essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Cryo-electron microscopy analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3-megadalton ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Our structure shows how UBR4 binds substrate and extends lysine-48-specific ubiquitin chains. Efficient substrate targeting depends on both preubiquitination and specific N-degrons, with KCMF1 acting as a key substrate filter. The architecture of the E4 megacomplex is conserved across eukaryotes, but species-specific adaptations allow UBR4 to perform its precisely tuned quality control function in diverse cellular environments.

PubMed: 40875847
DOI: 10.1126/science.adv9309

Experimental method

X-RAY DIFFRACTION (1.5 Å)