| abstract |
PROBLEM TO BE SOLVED: To provide a modified symmetry capable of binding to a TNFR1 receptor and diminishing signal transduction from it, which can be used in the treatment and / or prevention of diseases associated with soluble TNFα / TNFR1 interactions. Provided is a novel and stable trimmer TNFα structure having. Membrane-bound TNFα is unaffected by its ability to signal through TNFR2 and therefore does not significantly increase the risk of infection or malignancy, a new structure of TNFα can be used in treatment. An asymmetric TNFα trimmer of a protein subunit that optionally comprises the amino acid sequence of SEQ ID NO: 36, or the corresponding sequence, for use in therapeutic methods performed on the human or animal body. , Reference structure compound, as determined by X-ray crystallography 34. For all subunits within 0.9 Å RMSD of the same atom of pdb, residues 12-18, 47-50, 54-64, 76-82, 91-97, 117- of SEQ ID NO: 36, or corresponding sequences. The TNFα trimmer which employs conformations containing 125, 129 to 137, and 150 to 156 Cα atoms and can bind to TNFR1, but the signaling from the bound TNFR1 is attenuated or antagonized. [Selection diagram] None |