Functional analysis of tumour necrosis factor-α-related apoptosis-inducing ligand (TRAIL):: cysteine-230 plays a critical role in the homotrimerization and biological activity of this novel tumoricidal cytokine

We have determined that the mutation of the cysteine-230 residue to either glycine or serine in TRAIL (tumour necrosis factor-a-related apoptosis-inducing ligand) results in the formation of a structurally incompetent dimer and a consequent loss of apoptotic activity. Similarly, chemical modification of the thiol residues present in both reduced and Zn2+-depleted trimer converts TRAIL into an inactive dimer. We postulate that cysteine-230 plays a critical role in homotrimerization of this tumoricidal cytokine.