SOLUTION STRUCTURE OF CINC GRO INVESTIGATED BY HETERONUCLEAR NMR/

Cytokine-induced neutrophil chemoattractant (CINC/Gro) is a chemotacti c factor for neutrophils in the rat and a member of the CXC chemokine family, The refined three-dimensional structure of CINC/Gro was derive d With the aid of heteronuclear magnetic resonance spectroscopy and a hybrid method of distance geometry and simulated annealing, The backbo ne atomic r.m.s. differences for 19 structures about the mean coordina tes for residues 7 to 70 are 0.69+/-0.15 Angstrom for the dimer and 0. 56+/-0.13 Angstrom for the monomer, The N terminal region containing a n ELR sequence, an essential motif for chemotactic activity, is disord ered in solution, as in other CXC chemokines, The dimer structure cons ists of a six-stranded anti-parallel beta sheet with two C-terminal al pha helices on the beta sheet, The overall dimer structure of CINC/Gro is similar to that of human MGSA, though the backbone r.m.s.d.s betwe en CINC/Gro and the two MGSA structures were high (1.81 and 2.34 Angst rom for the monomer) in spite of the high sequence homology (67%), The major difference resides in the relative position of the C-terminal a lpha helix with respect to the beta sheet, This results in a differenc e of interhelical distances in the dimer: wider (15 Angstrom) in CINC/ Gro, as in IL-8, than in MGSA (11.7 and 10 Angstrom).