9QWZ
Cryo-EM structure of the human UBR4/KCMF1/CALM1 complex (BP focused refinement)
This is a non-PDB format compatible entry.
Summary for 9QWZ
| Entry DOI | 10.2210/pdb9qwz/pdb |
| EMDB information | 53431 |
| Descriptor | E3 ubiquitin-protein ligase KCMF1, E3 ubiquitin-protein ligase UBR4 (2 entities in total) |
| Functional Keywords | ubiquitin ligase, protein quality control, ligase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 619036.65 |
| Authors | Grabarczyk, D.B.,Clausen, T. (deposition date: 2025-04-15, release date: 2025-09-03, Last modification 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 Cited by 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: 40875847DOI: 10.1126/science.adv9309 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.8 Å) |
Structure validation
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