Related Experiment Video
Updated: Feb 28, 2026

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
Functional interfaces between TICAM-2/TRAM and TICAM-1/TRIF in TLR4 signaling
Kenji Funami1, Misako Matsumoto2, Hiroyuki Oshiumi2,3
1Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan kfunami@med.hokudai.ac.jp seya-tu@pop.med.hokudai.ac.jp.
Abstract:
Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS), produces pro-inflammatory cytokines and type I interferons, and associates with a trigger of endotoxin shock. TLR4 is interacted with a TIR domain-containing adaptor molecule-2 (TICAM-2)/TRAM [TRIF (TIR domain-containing adaptor-inducing interferon-β)-related adaptor molecule] via its Toll-interleukin-1 receptor homology (TIR) domain. TICAM-2 acts as a scaffold protein and activates TIR domain-containing adaptor molecule-1 (TICAM-1)/TRIF. According to the structural analysis by NMR, TICAM-2 interacts with TICAM-1 by the acidic amino acids motif, E87/D88/D89. The TIR domain of TICAM-2 couples with the dimer of TIR domain of TLR4 beneath the membrane, and TICAM-2 itself also forms dimer and constitutes a binding site with TICAM-1. Endosomal localization of TICAM-2 is essential for TLR4-mediated type I interferon-inducing signal from the endosome. N-terminal myristoylation allows TICAM-2 to anchor to the endosomal membrane. Additionally, we have identified two acidic amino acids, D91/E92, as a functional motif that cooperatively determines endosomal localization of TICAM-2. This structural information of TICAM-2 suggests that the specific structure is indispensable for the endosomal localization and type I interferon production of TICAM-2. Taken together with the knowledge on cytoplasmic sensors for LPS, TICAM-2/TICAM-1 may conform to a signal network on TLR4 to facilitate induction of cytokine disorders.
More Related Videos
06:15Characterization of Thymus-dependent and Thymus-independent Immunoglobulin Isotype Responses in Mice Using Enzyme-linked Immunosorbent Assay
Published on: September 7, 2018
09:51Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
Related Concept Videos
Cotranslational Protein Translocation
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Intracellular Signaling Affects Focal Adhesions
Some...
Tight Junctions
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...
Tail-anchoring of Proteins in the ER Membrane