MODULARITY IN THE TNF-RECEPTOR FAMILY

Tumour necrosis factor (TNF) receptor family members regulate processe s that range from cell proliferation to programmed cell death, The ext racellular, ligand-binding domains of these proteins consist of small, cysteine-rich subdomains, first observed in the three-dimensional str uctures of the type I TNF receptor, A structure-based alignment of TNF R family members indicates that the extracellular domains are construc ted primarily of two small polypeptide modules. These modules play dis tinctive structural roles in the architecture of the domains, Analogue s of at least one of these modules can be found in the domains of othe r receptors and extracellular proteins, Variations in their sequence a nd order of assembly are expected to account for differences in shape, flexibility and ligand specificity.