A homology-derived structural model of the murine macrophage inflammatory protein, MIP-1 alpha.

Macrophage inflammatory protein 1 alpha (MIP-1 alpha), a monocyte cytokine, has roles postulated for it in neutrophil chemoattraction, the inflammatory response and the control of haemopoietic stem cell proliferation. The three-dimensional structure of MIP-1 alpha has been modelled structurally, based on its sequence similarity to interleukin-8 and related proteins. The predicted dimeric form of MIP-1 alpha contains two symmetry-related antiparallel alpha-helices lying at an angle across a beta-sheet. The interhelical region and the beta-sheet flooring it are discussed as the potential receptor-binding site in terms of the distribution of negatively charged amino-acid side-chains, which contrasts remarkably with the corresponding positively-charged locations for IL-8. The general topographical features of this (alpha + beta) structural family of cytokines and related proteins (including HLA-A2, PF-4) are discussed. The members of this cytokine family fall into two structural groups as the antiparallel helices (N to C directed) mounted across the beta-sheet platform can be located in a clockwise (e.g. HLA-A2) or anticlockwise (e.g. MIP-1 alpha) sense with respect to the beta-floor).