title: High-resolution three-dimensional structure of interleukin 1 beta in solution by three- and four-dimensional nuclear magnetic resonance spectroscopy.
abstract: 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 (13C and 15N) 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 A for the backbone atoms and 0.82 +/- 0.04 A 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 A. 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.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: G M
authors.initials: GM
authors.lastname: Clore
authors.forename: P T
authors.initials: PT
authors.lastname: Wingfield
authors.forename: A M
authors.initials: AM
authors.lastname: Gronenborn
mesh_terms: D000595:Amino Acid Sequence; D002151:Calorimetry; D002247:Carbon Isotopes; D007375:Interleukin-1 / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D011487:Protein Conformation; D012996:Solutions
chemical_list: D002247:Carbon Isotopes; D007375:Interleukin-1; D009587:Nitrogen Isotopes; D012996:Solutions