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. 2000 Nov;59(Suppl 1):i50–i53. doi: 10.1136/ard.59.suppl_1.i50

The pre-ligand binding assembly domain: a potential target of inhibition of tumour necrosis factor receptor function

F K Chan
PMCID: PMC1766631  PMID: 11053089

Abstract

Signalling by the tumour necrosis factor receptors (TNFR) is thought to be mediated by the binding of the trimeric ligand TNF to three monomeric subunits of the receptor. This ligand induced trimerisation model of TNFR signalling is mainly supported by crystallographic data of the p60 TNFR-1 and TNFβ complex in which the trimeric ligand interdigitates between the individual receptor chains and prevents the receptor subunits from interacting with each other. Recently, a domain NH2-terminal to the ligand binding domain in the extracellular region of p60 TNFR-1, p80 TNFR-2 and Fas was identified that mediates receptor self association before ligand binding. This pre-ligand binding assembly domain or PLAD is critical for assembly of functional receptor complexes on the cell surface and may provide a potential target in the design of future novel therapeutics against diseases mediated by members of the TNFR family of receptors.



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Figure 1  .

Figure 1  

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The two models of TNFR signalling. The ligand induced trimerisation model (top) and the pre-ligand assembly model (bottom). The NH2-terminal PLAD domain and the ligand binding domain are shown.

Selected References

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