5xme

Publication Abstract from PubMed

The TNFR1-associated death domain protein (TRADD) is an intracellular adaptor protein involved in various signaling pathways, such as antiapoptosis. Its C-terminal death domain (DD) is responsible for binding other DD-containing proteins including the p75 neurotrophin receptor (p75NTR). Here we present a solution structure of TRADD DD derived from high-resolution NMR spectroscopy. The TRADD DD comprises two super-secondary structures, an all-helix Greek key motif and a beta-hairpin motif flanked by two alpha helices, which make it unique among all known DD structures. The beta-hairpin motif is essential for TRADD DD to fold into a functional globular domain. The highly-charged surface suggests a critical role of electrostatic interactions in TRADD DD-mediated signaling. This novel structure represents a new class within the DD superfamily and provides a structural basis for studying homotypic DD interactions. NMR titration revealed a direct weak interaction between TRADD DD and p75NTR DD monomers. A binding site next to the p75NTR DD homodimerization interface indicates that TRADD DD recruitment to p75NTR requires separation of the p75NTR DD homodimer, explaining the mechanism of NGF-dependent activation of p75NTR-TRADD-mediated antiapoptotic pathway in breast cancer cell.

Structure of the C-terminal domain of TRADD reveals a novel fold in the death domain superfamily.,Zhang N, Yuan W, Fan JS, Lin Z Sci Rep. 2017 Aug 1;7(1):7073. doi: 10.1038/s41598-017-07348-9. PMID:28765645^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.