Solution structure of the tumor necrosis factor receptor-1 death domain

Steven F. Sukits, Lih Ling Lin, Sang Hsu, Karl Malakian, Robert Powers, Guang Yi Xu

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Tumor necrosis factor receptor-1 death domain (TNFR-1 DD) is the intracellular functional domain responsible for the receptor signaling activities. The solution structure of the R347K mutant of TNFR-1 DD was solved by NMR spectroscopy. A total of 20 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1167 distance constraints and 117 torsion angle constraints. The atomic rms distribution about the mean coordinate positions for the 20 structures for residues composing the secondary structure region is 0.40 Å for the backbone atoms and 1.09 Å for all atoms. The structure consists of six antiparallel α-helices arranged in a similar fashion to the other members of the death domain superfamily. The secondary structure and three-dimensional structure of R347K TNFR1-DD are very similar to the secondary structure and deduced topology of the R347A TNFR1-DD mutant. Mutagenesis studies identified critical residues located in α2 and part of α3 and α4 that are crucial for self-interaction and interaction with TRADD. Structural superposition with previously solved proteins in the death domain superfamily reveals that the major differences between the structures reside in α2, α3, and α4. Interestingly, these regions correspond to the binding sites of TNFR1-DD, providing a structural basis for the specificity of death domain interactions and its subsequent signaling event.

Original languageEnglish (US)
Pages (from-to)895-906
Number of pages12
JournalJournal of Molecular Biology
Volume310
Issue number4
DOIs
StatePublished - Jul 20 2001

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Receptors, Tumor Necrosis Factor, Type I
Tumor Necrosis Factor Receptors
Mutagenesis
Magnetic Resonance Spectroscopy
Binding Sites
Death Domain
Proteins
Death Domain Superfamily

Keywords

  • Apoptosis
  • Death domain
  • NMR
  • Structure
  • TNFR-1

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Solution structure of the tumor necrosis factor receptor-1 death domain. / Sukits, Steven F.; Lin, Lih Ling; Hsu, Sang; Malakian, Karl; Powers, Robert; Xu, Guang Yi.

In: Journal of Molecular Biology, Vol. 310, No. 4, 20.07.2001, p. 895-906.

Research output: Contribution to journalArticle

Sukits, Steven F. ; Lin, Lih Ling ; Hsu, Sang ; Malakian, Karl ; Powers, Robert ; Xu, Guang Yi. / Solution structure of the tumor necrosis factor receptor-1 death domain. In: Journal of Molecular Biology. 2001 ; Vol. 310, No. 4. pp. 895-906.
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