Tumor Necrosis Factor-beta with its Receptor

The picture below shows one TNF-beta monomer associated with the 55 kd TNF receptor, also known as TNF-R55. It has been shown that, in solution, TNF receptors form complexes with TNF where three receptor molecules binding to one TNF trimer (Loetscher, 1991; Schoenfeld, 1991). To see a static picture of this, check out SCOP.

The structure of sTNF-R55, which is only the extracellular region of TNF-R55, is very interesting. It contains all four of the sequence domains that are characterized by the 6-cysteine repeat motif (Eck, 1993). Click the button to investigate! This motif identifies members of the nerve growth factor (NGF)/TNF receptor gene family (Eck, 1993). Of the 12 receptors in the TNF Receptor superfamily, TNF-R55 is most homologous to TNF-R75. Each of these receptors can bind TNF-alpha or TNF-beta (Smith, 1994). The 6 cysteine residues form three disulfide bridges which are arranged like the rungs of a ladder. Click here to see a picture of this in SCOP.

As you can see to the right , the sTNF-R55 molecules, in complex with TNF-beta, are long and narrow. They bind with their axes almost parallel to the 3 fold axis of the TNF trimer (Eck, 1993). To see this in SCOP, click here. At the bottom of the TNF-beta trimer, the N-terminal region of sTNF-R55 binds to the shallow groove that was described previously for the TNF-alpha molecule (Eck, 1993). The sTNF-R55 molecule also contacts one of the TNF subunits in the central region of the molecule. At the top of this complex, the C-terminal part of sTNF-R55 interacts with both TNF monomers. In a cell, the membrane spanning sequence of a full TNF receptor is C-terminal to the sTNF-R55 sequence (Eck, 1993).

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Heather Sarauer
Department of Chemistry
University of Wisconsin--Eau Claire

sarauehl@uwec.edu