The intracellular domain of the low affinity p75 nerve growth factor receptor is a death effector domain

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.