Related Experiment Video

Updated: Mar 1, 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

15.9K

Structure-activity relationship of the p55 TNF receptor death domain and its lymphoproliferation mutants

G De Wilde1, J Murray-Rust, E Boone

  • 1Department of Molecular Biology, University of Gent-VIB, Belgium.

European Journal of Biochemistry
|March 7, 2001
PubMed

Insights

Tumor necrosis factor receptor (TNFR55) death domain (DD) structure was investigated using biophysical methods. Structural similarity to other death domains was found, explaining in vivo mutation effects.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biophysics

Background:

  • The TNF receptor (TNFR55) death domain (DD) is crucial for initiating cell death and gene expression.
  • Understanding TNFR55 DD structure is key to elucidating its biological functions.

Purpose of the Study:

  • To characterize the solution structure of the TNFR55 DD.
  • To compare TNFR55 DD structure with other known death domains.
  • To investigate the impact of specific mutations on TNFR55 DD structure and stability.

Main Methods:

  • Expression and purification of TNFR55 DD as a thioredoxin fusion protein.
  • Circular dichroism and fluorescence spectroscopy for structural analysis.
  • Homology modeling using FADD as a template.
  • Analysis of lymphoproliferation (lpr) mutations in vivo.

Main Results:

  • TNFR55 DD exhibits a fold similar to other known death domains in solution.
  • Homology modeling provided a 3-D structural model of TNFR DD.
  • Mutations (Leu351 to Ala and Leu351 to Asn) affected TNFR55 DD structure and stability.
  • Structural findings explain observed in vivo differences in lpr mutations.

Conclusions:

  • The structural characterization of TNFR55 DD provides insights into its function.
  • The study explains the differential effects of mutations on TNFR55 DD.
  • This work contributes to understanding TNF signaling pathways.

More Related Videos

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method16:07

Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody mAb by Neutralizing TNF Using an In Vitro Bioanalytical Method

Published on: September 16, 2017

9.7K
Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

11.9K

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.0K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.1K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.7K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.9K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
16.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K