9BID

human ZYG11B and EloginB/C complex

Summary for 9BID

• Entry DOI: 10.2210/pdb9bid/pdb
• EMDB information: 44588
• Descriptor: Protein zyg-11 homolog B, Elongin-B, Elongin-C (3 entities in total)
• Functional Keywords: gly/n degron, peptide binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 108454.54

Authors

Liu, X.,Gross, J.D. (deposition date: 2024-04-23, release date: 2026-03-18, Last modification date: 2026-10-07)

Primary citation

Liu, X.,Li, Y.,Castro, L.K.,Yu, Z.,Cheng, Y.,Daugherty, M.D.,Gross, J.D.
Structure of the E3 ligase CRL2 ZYG11B with substrates reveals the molecular basis for N-degron recognition and ubiquitination.
Cell Rep, 45:117401-117401, 2026

PubMed Abstract: ZYG11B is a substrate specificity factor for the cullin-2-RING ubiquitin ligase (CRL2), which plays a critical role in the recognition and degradation of Gly/N-degrons. Yet, how ZYG11B assembles with CRL2, and how ZYG11B couples specific substrate recognition to CRL2-mediated ubiquitination, is unknown. We present the cryo-electron microscopy (cryo-EM) structures of the CRL2 holoenzyme alone and in complex with a Gly/N-peptide from the inflammasome-forming pathogen sensor NLRP1. The structures indicate that ZYG11B folds into a leucine-rich repeat followed by two armadillo repeat domains that promote assembly with CRL2 and specific recognition of the NLRP1 Gly/N-degron that is revealed by viral protease cleavage. Our structural and functional data indicate that blocking ZYG11B recognition of the NLRP1 Gly/N-degron inhibits NLRP1 inflammasome activation by a viral protease. Overall, we show how the CRL2 E3 ligase complex recognizes Gly/N-degron substrates, including those that are involved in viral protease-mediated activation of the NLRP1 inflammasome.

PubMed: 42224082
DOI: 10.1016/j.celrep.2026.117401

Experimental method

ELECTRON MICROSCOPY (3.99 Å)