Work

Structural Insights into the Assembly of Large Oligomeric Signalosomes in the Toll-Like Receptor–Interleukin-1 Receptor Superfamily

Year: 2012

Type: review

Abstract: The Toll-like receptor (TLR)-interleukin 1 receptor (IL-1R) superfamily plays fundamentally important roles in innate immune and inflammatory responses. Structural studies have begun to show that upon ligand stimulation, TLRs and IL-1Rs assemble large oligomeric intracellular signaling complexes, or "signalosomes," to induce the activation of kinases and E3 ubiquitin ligases, leading eventually to the activation of the transcription factors that are responsible for the expression of genes whose products mediate immune and inflammatory responses. The different scaffolds identified by these structural studies provide a molecular foundation for understanding the formation of microscopically visible signaling clusters that have long been known to cell biologists. Here, we illustrate the potential mechanisms of step-by-step assembly from the membrane-proximal interactions to the more downstream events. Formation of large oligomeric signalosomes may help to establish a digital threshold response in TLR and IL-1R signaling.

Source: Science Signaling

DOI: 10.1126/scisignal.2003124

Authors: Ryan Ferrao, Jixi Li, Elisa Bergamin, Hao Wu

Institutions: Cornell University, Weill Cornell Medicine

Language: English

Topic: Immune Response and Inflammation

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: green

Funder: National Institute of Allergy and Infectious Diseases

Awards: Structural & Functional Studies of TLR/IL-1R Signaling, Structural and functional studies of the IkappaB kinase (IKK) complex, Structural and functional elucidation of the necrosome in innate immune signaling