title: A homology-derived structural model of the murine macrophage inflammatory protein, MIP-1 alpha.
abstract: 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).
authors.affiliation: Department of Pharmacy, University of Manchester, U.K.
authors.forename: J H
authors.initials: JH
authors.lastname: McKie
authors.forename: K T
authors.initials: KT
authors.lastname: Douglas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002645:Chickens; D016207:Cytokines / Q000737:chemistry* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D015846:Monokines / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013552:Swine
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D015789:HLA-A2 Antigen; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D006493:Heparin