3-DIMENSIONAL STRUCTURE OF INTERLEUKIN-8 IN SOLUTION

The solution structure of the interleukin 8 (IL-8) dimer has been solved by nuclear magnetic resonance (NMR) spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure determination is based on a total of 1880 experimental distance restraints (of which 82 are intersubunit) and 362 torsion angle restraints (comprising φ, ψ, and χ1 torsion angles). A total of 30 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 1-5 of each subunit) is 0.41 ± 0.08 Å for the backbone atoms and 0.90 ± 0.08 Å for all atoms. The three-dimensional solution structure of the IL-8 dimer reveals a structural motif in which two symmetry-related antiparallel α-helices, approximately 24 Å long and separated by about 14 Å, lie on top of a six-stranded antiparallel β-sheet platform derived from two three-stranded Greek keys, one from each monomer unit. The general architecture is similar to that of the α1/α2 domains of the human class I histocompatibility antigen HLA-A2. It is suggested that the two α-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices. © 1990, American Chemical Society. All rights reserved.