Related Experiment Video
Updated: Apr 3, 2026

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome
Jianping Liu1, Jing Zhao2,3, Jiayang Gao2,3
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China. jpliu@sioc.ac.cn.
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 fate1. 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 complexes2,3, 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.
More Related Videos
10:19Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin
Published on: January 24, 2025
08:55Single-Molecule Imaging of Lateral Mobility and Ion Channel Activity in Lipid Bilayers using Total Internal Reflection Fluorescence TIRF Microscopy
Published on: February 17, 2023
Related Concept Videos
Electric Dipoles and Dipole Moment
Theoretically, studying electric dipoles leads to understanding why the resultant electric forces around us are weak. Since electric forces are strong, remnant net charges are rare. Hence, the interaction between dipoles helps us understand electrical interactions in...
Tail-anchoring of Proteins in the ER Membrane
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Protein Translocation Machinery on the ER Membrane
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Intracellular Signaling Affects Focal Adhesions
Some...
Induced Electric Dipoles
Since the absolute value of potential energy holds no physical meaning, its zero value can be chosen as per...