SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN

Interleukin-1 receptor antagonist protein (IRAP) is a naturally occurr ing inhibitor of the interleukin-1 receptor. In contrast to IL-1 beta, IRAP binds to the IL-1 receptor but does not elicit a physiological r esponse. We have determined the solution structure of IRAP using NMR s pectroscopy. While the overall topology of the two 153-residue protein s is quite similar, functionally critical differences exist concerning the residues of the linear amino acid sequence that constitute struct urally homologous regions in the two proteins. Structurally homologous residues important for IL-1 receptor binding are conserved between IR AP and IL-1 beta. By contrast, structurally homologous residues critic al for receptor activation are not conserved between the two proteins.