9VIN

Ternary complex of TNFR1-DD, TRADD-DD and RIPK1-DD

Summary for 9VIN

• Entry DOI: 10.2210/pdb9vin/pdb
• EMDB information: 65094
• Descriptor: Tumor necrosis factor receptor type 1-associated DEATH domain protein, Receptor-interacting serine/threonine-protein kinase 1, Tumor necrosis factor receptor superfamily member 1A, membrane form (3 entities in total)
• Functional Keywords: tnfr1, ripk1, tradd, death domain, apoptosis
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 31
• Total formula weight: 411677.07

Authors

Liu, J.,Han, Y.,Zhao, J.,Gao, J.,Yuan, J. (deposition date: 2025-06-18, release date: 2026-04-08, Last modification date: 2026-04-15)

Primary citation

Liu, J.,Zhao, J.,Gao, J.,Zhao, K.,Han, Y.,Yang, J.,Li, Z.,Ye, J.,Sun, Z.,Wang, F.,Liu, X.,Li, Z.,Ji, S.,Liu, B.,Liu, C.,Zhang, Y.,Yuan, J.,Chou, J.J.
Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome.
Nature, 2026

PubMed Abstract: Dynamic assembly of the complex I signalosome mediated by three death domain (DD)-containing proteins-TNFR1, TRADD and RIPK1-is key for transmitting extracellular TNF stimuli to intracellular NF-κB signalling in controlling 'live or die' cell fate. This signalling hub features the rapid recruitment of TRADD and RIPK1 after engagement of TNFR1 by TNF for the formation of complex I, followed by timed disassembly for transition into downstream signalling complexes, but the mechanism driving the dynamic reversibility of complex I remains unclear. Here we captured the assembly core of complex I and determined its cryo-electron microscopy structure, showing a pentameric fibre comprising 31 DDs, with a single layer of a TRADD-DD pentamer sandwiched between multiple layers of TNFR1-DD and RIPK1-DD homopentamers. Structural analysis revealed a strong opposing electric dipole moment (EDM) generated by RIPK1-DD oligomerization relative to that of TNFR1-DD and TRADD-DD. Structure-guided mutagenesis in TNFR1-TRADD-RIPK1 pentameric fibres altering the EDM without affecting DD oligomerization demonstrated the role and mechanism of EDM in driving the dynamic reversibility mediating the rapid assembly and disassembly of complex I. Our study demonstrates a role for long-range interactions mediated by protein EDMs in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling.

PubMed: 41922760
DOI: 10.1038/s41586-026-10304-1

Experimental method

ELECTRON MICROSCOPY (3.41 Å)