Three-dimensional structures of alpha and beta chemokines.
Members of the chemokine family of proteins play a key role in the orchestration of the immune response. This family has been further divided into two subfamilies, alpha and beta, based on sequence, function, and chromosomal location. To date, the three-dimensional structures of two members of the alpha subfamily, interleukin-8 (IL-8) and platelet factor 4, and one member of the beta subfamily, human macrophage inflammatory protein-1 beta (hMIP-1 beta), have been solved by either NMR or X-ray crystallography. In this review, we discuss their three-dimensional structures and their possible relationship to function. The structures of the monomers are very similar, as expected from the significant degree of sequence identity between these proteins. The quaternary structures of the alpha and beta chemokines, however, are entirely distinct and the dimer interface is formed by a completely different set of residues. Whereas the IL-8 dimer is globular, the hMIP-1 beta dimer is elongated and cylindrical. Platelet factor 4 is a tetramer comprising a dimer of dimers of the IL-8 type. The IL-8 dimer comprises a six stranded anti-parallel beta-sheet, three strands contributed by each subunit, on top of which lie two antiparallel helices separated by approximately 14 A, and the symmetry axis is located between residues 26 and 26' (equivalent to residue 29 of hMIP-1 beta) at the center of strands beta 1 and beta 1'.(ABSTRACT TRUNCATED AT 250 WORDS)
Clore
G M
GM
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520.
Gronenborn
A M
AM
D000595:Amino Acid Sequence; D001665:Binding Sites; D054407:Chemokine CCL4; D016207:Cytokines / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry* / Q000502:physiology; D019402:Macrophage Inflammatory Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015846:Monokines / Q000737:chemistry* / Q000502:physiology; D010978:Platelet Factor 4 / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D054407:Chemokine CCL4; D016207:Cytokines; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D010978:Platelet Factor 4