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RAIDD is a new 'death' adaptor molecule

Abstract

THE effector arm of the cell-death pathway is composed of cysteine proteases belonging to the ICE/CED-3 family1,2. In metazoan cells these exist as inactive polypeptide precursors (zymogens), each composed of a prodomain, which is cleaved to activate the protease, and a large and small catalytic subunit. The coupling of these 'death' proteases to signalling pathways is probably mediated by adaptor molecules that contain protein–protein interaction motifs such as the death domain1. Here we describe such an adaptor molecule, RAIDD, which has an unusual bipartite architecture comprising a carboxy-terminal death domain that binds to the homologous domain in RIP, a serine/threonine kinase component of the death pathway3,4. The amino-terminal domain is surprisingly homologous with the sequence of the prodomain of two ICE/CED-3 family members, human ICH-1 (ref. 5) and Caenorhabditis elegans CED-3 (ref. 6). This similar region mediates the binding of RAIDD to ICH-1 and CED-3, serving as a direct link to the death proteases, indicating that the prodomain may, through homophilic interactions, determine the specificity of binding of ICE/CED-3 zymogens to regulatory adaptor molecules. Finally, alternations in the sequence of the N-terminal domain that are equivalent to inactivating mutations in the C. elegans ced-3 gene7,8 prevent homophilic binding, highlighting the potentially primordial nature of this interaction.

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Duan, H., Dixit, V. RAIDD is a new 'death' adaptor molecule. Nature 385, 86–89 (1997). https://doi.org/10.1038/385086a0

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