Human CC chemokine I-309, structural consequences of the additional disulfide bond

I-309 is a member of the CC subclass of chemokines and is one of only three human chemokines known to contain an additional, third disulfide bond. The three-dimensional solution structure of I-309 was determined by H-1 nuclea r magnetic resonance spectroscopy and dynamic simulated annealing. The stru cture of I-309, which remains monomeric at high concentrations, was determi ned on the basis of 978 experimental restraints. The N-terminal region of I -309 was disordered, as has been previously observed for the CC chemokine e otaxin but not others such as MCP-1 and RANTES. This was followed in I-309 by a well-ordered region between residues 13 and 69 that consisted of a 3(1 0)-helix, a triple-stranded antiparallel beta-sheet, and finally a C-termin al alpha-helix. Root-mean-square deviations of 0.61 and 1.16 were observed for the backbone and heavy atoms, respectively. A comparison of I-309 to eo taxin and HCC-2 revealed a significant structural change in the C-terminal region of the protein. The alpha-helix normally present in chemokines was t erminated early and was followed by a short section of extended strand. The se changes were a direct result of the additional disulfide bond present in this protein. An examination of the I-309 structure will aid in an underst anding of the specificity of this protein with its receptor, CCR8.