HIGH-RESOLUTION 3-DIMENSIONAL STRUCTURE OF INTERLEUKIN-1-BETA IN SOLUTION BY 3-DIMENSIONAL AND 4-DIMENSIONAL NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

The determination of the high-resolution three-dimensional solution structure of interleukin 1-beta (IL-1-beta), a protein of 153 residues and 17.4 kDa, which plays a central role in the immune and inflammatory responses, has been determined by heteronuclear (C-13 and N-15) three- and four-dimensional NMR spectroscopy. The structure is based on 3146 experimental restraints comprising 2780 distance and 366 torsion angle (phi, psi, and chi-1) restraints. A total of 32 simulated annealing structures are calculated, and the atomic RMS distribution about the mean coordinate positions is 0.41 +/- 0.04 angstrom for the backbone atoms and 0.82 +/- 0.04 angstrom for all atoms (excluding residue 1 at the N-terminus and residues 152 and 153 at the C-terminus, which are partially disordered). In the case of internal side chains with a surface accessibility of less-than-or-equal-to 40%, the atomic RMS distribution about the mean coordinate positions for all atoms is 0.49 +/- 0.03 angstrom. IL-1-beta resembles a tetrahedron and is composed of 12-beta-strands arranged in three pseudosymmetric topological units, each of which comprises 5 strands. Analysis of the mutational data on IL-1-beta in the light of the three-dimensional structure suggests the presence of three distinct binding sites for the IL-1 receptor on the surface of the protein. It is suggested that each of the three immunoglobulin domains which comprise the extracellular portion of the IL-1 receptor recognizes one of these sites.