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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 phi, psi, and chi 1
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 A for the backbone atoms and 0.90
+/- 0.08 A for all atoms. The three-dimensional solution structure of the IL-8
dimer reveals a structural motif in which two symmetry-related antiparallel
alpha-helices, approximately 24 A long and separated by about 14 A, lie on top
of a six-stranded antiparallel beta-sheet platform derived from two
three-stranded Greek keys, one from each monomer unit. The general architecture
is similar to that of the alpha 1/alpha 2 domains of the human class I
histocompatibility antigen HLA-A2. It is suggested that the two alpha-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.
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