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TNF alpha and the TNF receptor superfamily: structure-function relationship(s)
1Centre for Biomolecular Sciences, The University, St. Andrews, Fife KY16 9ST, Scotland, United Kingdom.
Microscopy Research and Technique
|July 13, 2000
Summary
Tumour Necrosis Factor alpha (TNF alpha), an inflammatory cytokine, triggers cell death and aids in fighting infections and cancer. Its structure and interactions with its receptor superfamily are crucial for these diverse biological roles.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- Tumour Necrosis Factor alpha (TNF alpha) is a key inflammatory cytokine.
- It mediates diverse cellular signaling pathways, including necrosis and apoptosis.
- TNF alpha is vital for host defense against infections and cancers.
Purpose of the Study:
- To review structure/function relationships of TNF alpha and its receptor superfamily.
- To explore how structural features contribute to TNF alpha's diverse effects.
Main Methods:
- Crystallography was used to define the structures of TNF alpha, TNF beta, TNFR-1 extracellular domain (sTNFR-1), and the TNF beta-sTNFR-1 complex.
- Review of existing literature on TNF alpha and its receptor superfamily.
Main Results:
- TNF alpha binds as a trimer to TNFR-1 and TNFR-2 receptors.
- The TNF receptor superfamily, including FAS, CD40, CD27, and RANK, share cysteine-rich extracellular domains.
- Decoy receptors can sequester TNF molecules, preventing apoptosis.
Conclusions:
- Structural insights into TNF alpha and its receptors are essential for understanding its pleiotropic functions.
- The interaction between TNF alpha and its receptors dictates cellular responses like necrosis and apoptosis.