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The structure of tumour necrosis factor--implications for biological function.
E Y Jones1, D I Stuart, N P Walker
1Laboratory of Molecular Biophysics, University of Oxford, UK.
Journal of Cell Science. Supplement
|January 1, 1990
Summary
The three-dimensional structure of Tumor Necrosis Factor (TNF) was determined using X-ray crystallography. This reveals TNF
Area of Science:
- Structural Biology
- Protein Crystallography
- Immunology
Background:
- Tumor Necrosis Factor (TNF) is a critical cytokine involved in immune responses.
- Understanding TNF's structure is key to elucidating its function and interactions.
- Previous studies relied on mutagenesis and antibody binding data without structural context.
Purpose of the Study:
- To determine the high-resolution three-dimensional structure of TNF.
- To correlate structural findings with existing functional data (mutagenesis, antibody binding).
- To identify regions of biological significance within the TNF structure.
Main Methods:
- X-ray crystallography was employed to resolve the TNF structure.
- The structure was determined at a resolution of 0.29 nm.
- Analysis involved comparing TNF structure with known protein motifs.
Main Results:
- TNF forms a compact trimer from three identical 157-amino acid subunits.
- Each subunit exhibits a 'jelly roll' beta-sandwich fold, previously seen in viral proteins.
- Subunits associate via edge-to-face packing around a threefold axis, forming a conical structure.
- Conserved residues between TNF and lymphotoxin suggest similar structural motifs and association.
Conclusions:
- The determined TNF structure provides a framework for interpreting mutagenesis and antibody binding data.
- The 'jelly roll' motif is present in TNF, a non-viral protein.
- A biologically important region is identified at the interface between subunits on the trimer's lower half.