Solution structure of the human CC chemokine 2: A monomeric representativeof the CC chemokine subtype

HCC-2, a 66-amino acid residue human CC chemokine, was reported to induce c hemotaxis on monocytes, T-lymphocytes, and eosinophils. The three-dimension al, structure of HCC-2 has been determined by H-1 nuclear magnetic resonanc e (NMR) spectroscopy and restrained molecular dynamics calculations on the basis of 871 experimental restraints. The structure is well-defined, exhibi ting average root-mean-square deviations of 0.58 and 0.96 Angstrom for the backbone heavy atoms and all heavy atoms of residues 5-63, respectively. In contrast to most other chemokines, subtle structural differences impede di mer formation of HCC-2 in a concentration range of 0.1 mu M to 2 mM. HCC-2, however, exhibits the same structural elements as the other chemokines, i. e., a triple-stranded antiparallel beta-sheet covered by an alpha-helix, sh owing that the chemokine fold is not influenced by quaternary interactions. Structural investigations with a HCC-2 mutant prove that a third additiona l disulfide bond present in wild-type HCC-2 is not necessary for maintainin g the relative orientation of the helix and the beta-sheet.