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

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Abstract

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
Volume300
Issue number5
DOIs
StatePublished - Jul 28 2000

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Tumor Necrosis Factor Receptors
Mutant Proteins
Mutagenesis
Death Domain

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Telliez, J. B., Xu, G. Y., Woronicz, J. D., Hsu, S., Wu, J. L., Lin, L., ... 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. https://doi.org/10.1006/jmbi.2000.3899

Mutational analysis and NMR studies of the death domain of the tumor necrosis factor receptor-1. / Telliez, Jean Baptiste; Xu, Guang Yi; Woronicz, John D.; Hsu, Sang; Wu, Jing Lun; Lin, Laura; Sukits, Steven F.; Powers, Robert; Lin, Lih Ling.

In: Journal of Molecular Biology, Vol. 300, No. 5, 28.07.2000, p. 1323-1333.

Research output: Contribution to journalArticle

Telliez, JB, Xu, GY, Woronicz, JD, Hsu, S, Wu, JL, Lin, L, Sukits, SF, Powers, R & Lin, LL 2000, 'Mutational analysis and NMR studies of the death domain of the tumor necrosis factor receptor-1', Journal of Molecular Biology, vol. 300, no. 5, pp. 1323-1333. https://doi.org/10.1006/jmbi.2000.3899
Telliez, Jean Baptiste ; Xu, Guang Yi ; Woronicz, John D. ; Hsu, Sang ; Wu, Jing Lun ; Lin, Laura ; Sukits, Steven F. ; Powers, Robert ; Lin, Lih Ling. / Mutational analysis and NMR studies of the death domain of the tumor necrosis factor receptor-1. In: Journal of Molecular Biology. 2000 ; Vol. 300, No. 5. pp. 1323-1333.
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