The death domain superfamily, comprising the death domain, death effector domain, caspase recruitment domain and pyrin domain subfamilies, is one of the largest classes of protein interaction modules, and plays a particularly critical function in the assembly and activation of apoptotic and inflammatory complexes. Members of the death domain superfamily share a common structural feature, the 6-helical bundle fold. However, individual subfamilies exhibit distinct structural and sequence characteristics. The most distinct feature identified in structural studies is that only the death effector domain contains a charge triad, which is formed by the E/D-RxDL motif. However, using sequence alignment and structural comparison, in the present study we found that the p75-NGFR death domain also contains a charge triad. We therefore suggest that the p75-NGFR death domain should be classified as belonging to the death effector domain.

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