Mutational analysis and NMR studies of the death domain of the tumor necrosis factor receptor-1

Jean Baptiste Telliez, Guang Yi Xu, John D. Woronicz, Sang Hsu, Jing Lun Wu, Laura Lin, Steven F. Sukits, Robert Powers, Lih Ling Lin

Research output: Contribution to journalArticle

30 Scopus citations


Tumor necrosis factor receptor-1 (TNFR-1) death domain (DD) is the intracellular functional domain responsible for the receptor signaling activities. To understand the transduction mechanism of TNFR-1 signaling we performed structural and functional analysis of the TNFR-DD. The secondary structure of the TNFR-DD shows that it consists of six anti-parallel α-helices. The determination of the topological fold and an extensive mutagenesis analysis revealed that there are two opposite faces that are involved in self-association and interaction with the TRADD death domain. Interestingly, the same critical residues in TNFR-DD are involved in both interactions. There is a good correlation between the binding activities of the mutant proteins and their cytotoxic activities. These results provide important insight into the molecular interactions mediating TNFR-DD self-association and subsequent recruitment of TRADD in the signaling activity of TNFR-1. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)1323-1333
Number of pages11
JournalJournal of Molecular Biology
Issue number5
StatePublished - Jul 28 2000



  • Death domain
  • Mutagenesis
  • Secondary structure
  • TNFR-1
  • Topology

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Telliez, J. B., Xu, G. Y., Woronicz, J. D., Hsu, S., Wu, J. L., Lin, L., Sukits, S. F., Powers, R., & Lin, L. L. (2000). Mutational analysis and NMR studies of the death domain of the tumor necrosis factor receptor-1. Journal of Molecular Biology, 300(5), 1323-1333.