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Updated: Oct 2, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain

Kiyoshi Miki1, Edward M Eddy

  • 1Gamete Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.

Molecular and Cellular Biology
|March 23, 2002
PubMed

Insights

Silencer of death domain (SODD) regulates tumor necrosis factor receptor type 1 (TNFR1) aggregation and signaling. SODD acts as a cofactor, modulating TNFR1

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Self-aggregation of tumor necrosis factor receptor type 1 (TNFR1) triggers cell death pathways.
  • Silencer of death domain (SODD) is hypothesized to prevent TNFR1 self-aggregation.

Purpose of the Study:

  • To elucidate the molecular mechanism by which SODD regulates TNFR1 aggregation and signaling.
  • To investigate the role of ATP in TNFR1-SODD interactions and TNFR1 function.

Main Methods:

  • Co-immunoprecipitation assays to determine protein-protein interactions.
  • ATPase assays and point mutation analysis to characterize TNFR1's enzymatic activity.
  • In vitro aggregation and disassembly assays.

Main Results:

  • SODD binds to both Hsp70 and TNFR1 via its BAG domain.
  • ATP binding regulates SODD's interaction with Hsp70 and TNFR1, indicating TNFR1 possesses ATPase activity.
  • TNFR1 forms aggregates in ATP-depleted conditions, and SODD disassembles these aggregates in an ATP-dependent manner.

Conclusions:

  • SODD functions as an ATP-dependent cofactor, similar to BAG-1, modulating TNFR1's ATPase cycle.
  • A nucleotide-dependent conformational change in TNFR1 is proposed to be critical for regulating TNF signaling pathways.

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