HIGH-RESOLUTION SOLUTION STRUCTURE OF THE BETA-CHEMOKINE HMIP-1-BETA BY MULTIDIMENSIONAL NMR

The three-dimensional structure of a member of the beta subfamily of c hemokines, human macrophage inflammatory protein-1 beta (hMIP-1 beta), has been determined with the use of solution multidimensional heteron uclear magnetic resonance spectroscopy. Human MIP-1 beta is a symmetri c homodimer with a relative molecular mass of similar to 16 kilodalton s. The structure of the hMIP-1 beta monomer is similar to that of the related alpha chemokine interleukin-8 (IL-8). However, the quaternary structures of the two proteins are entirely distinct, and the dimer in terfaceis formed by a completely different set of residues. Whereas th e IL-8 dimer is globular, the hMIP-1 beta dimer is elongated and cylin drical. This provides a rational explanation for the absence of cross- binding and reactivity between the alpha and beta chemokine subfamilie s. Calculation of the solvation free energies of dimerization suggests that the formation and stabilization of the two different types of di mers arise from the burial of hydrophobic residues.