The molecular architecture of the TNF superfamily

Ligands of the TNF (tumour necrosis factor) superfamily have pivotal roles in the organization and function of the immune system, and are implicated in the aetiology of several acquired and genetic diseases. TNF ligands share a common structural motif, the TNF homology domain (THD), which binds to cysteine-rich domains (CRDs) of TNF receptors. CRDs are composed of structural modules, whose variation in number and type confers heterogeneity upon the family. Protein folds reminiscent of the THD and CRD are also found in other protein families, raising the possibility that the mode of interaction between TNF and TNF receptors might be conserved in other contexts.