Tumor Necrosis Factor

To the right is the structure of TNF-alpha which was determined at 2.6 angstrom resolution by x-ray crystallography (Eck, 1989). In solution TNF exists mainly as a trimer, which is how it is pictured now. Click here to see one of the17,350 Da monomers. This monomer is a "jelly-roll" beta-sheet sandwich which is composed almost entirely of antiparallel beta-sheets (Eck, 1989). Click here to investigate! You can adjust the size of the image by holding down the shift key and, at the same time, holding down your mouse button while moving the mouse. The beta-sandwich is composed of 10 beta-strands which can be seen in the topology diagram (Eck, 1989).

Strands a, h, c, and f make up the flat, inner sheet of the jelly roll and are involved in trimer contacts. Notice that the amino and carboxy strands are packed together in the inner sheet. The higly curved, outer sheet is made up of strands b, g, d, and e which form the outer surface of the trimer. Strand b in this outer sheet is interrupted, which is unusual in a beta-sandwich, at its amino terminus (residue 26) with a 20 amino acid chain that forms strands a1 and b1. These two strands surround the two sheets at the amino terminal edge and provide stability to this structure (Eck, 1989).

There are three helical segments in the TNF-alpha monomer, only one can be seen to the right in magenta. None of the helices extend more than one full term. Residues making up these helices are 106-110, 138-142, and 145-150 (Eck, 1989).

The TNF-alpha monomer also contains a disulfide bridge that serves as a connection between the loop connecting strands c and d with the loop conecting strands e and f. Residues 69 and 107 form this disulfide bond (Eck, 1989). Click here to see!

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Heather Sarauer
University of Wisconsin--Eau Claire

sarauehl@uwec.edu