33HM

Murine RNF213 (Y434A)

Summary for 33HM

• Entry DOI: 10.2210/pdb33hm/pdb
• EMDB information: 59444
• Descriptor: E3 ubiquitin-protein ligase RNF213, ADENOSINE-5'-TRIPHOSPHATE, ZINC ION (3 entities in total)
• Functional Keywords: e3 ubiquitin ligase, aaa+ atpase, cbm20, sugar binding protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 589827.50

Authors

Yip, M.C.J.,Naydenova, K.,Randow, F. (deposition date: 2026-08-16, release date: 2026-09-23, Last modification date: 2026-09-30)

Primary citation

Yip, M.C.J.,Naydenova, K.,Otten, E.G.,Heatley, A.,Moe, A.,Anton, L.,de Los Reyes-Ramirez, L.,Jolin, H.E.,Langevin, F.,Wiacek, M.,Franco, C.,Bertolotti, A.,Kukulski, W.,McKenzie, A.N.J.,Randow, F.
Quality control of glycogen through direct ubiquitylation by RNF213.
Nature, 2026

PubMed Abstract: Quality control of biomolecules is vital for organismal health. While DNA repair and protein quality control are well understood, how cells monitor other important biomolecules such as glycogen remains ill-defined. The accumulation of aberrant, poorly branched glycogen into insoluble polyglucosan bodies causes severe disease. Here, we discover autophagy of ubiquitylated aberrant glycogen as a previously unrecognized quality control mechanism safeguarding the brain from polyglucosan buildup. This mechanism depends on the E3 ubiquitin ligase RNF213. Mice lacking ligase activity in RNF213 accumulate polyglucosan in cerebellum, pons, and hippocampus. Using cells engineered to produce polyglucosan, we show that RNF213 selectively ubiquitylates abnormal glycogen. Cryo-EM analysis of RNF213 bound to glycogen-derived maltoheptaose revealed its CBM20 domain binds linear oligosaccharides. Disrupting carbohydrate binding results in gain of E3 ligase activity towards physiological glycogen, indicating the CBM20 domain limits RNF213 activity towards physiological glycogen. Epistasis analysis places RNF213 upstream of LUBAC, suggesting a hierarchical network of multiple E3 ligases surveying glycogen quality. Ubiquitylated polyglucosan recruits the autophagy receptors SQSTM1, TAX1BP1, and optineurin, thereby triggering uptake into autophagosomes. These findings identify RNF213 as a quality control factor preventing polyglucosan accumulation in astrocytes through direct ubiquitylation of polyglucosan, revealing an essential role for non-protein ubiquitylation in glycogen quality control.

PubMed: 42744304
DOI: 10.1038/s41586-026-11139-6

Experimental method

ELECTRON MICROSCOPY (3.1 Å)