The High Resolution NMR Solution Structure of Monocyte Chemoattractant Protein-3

Abstract

The high resolution solution structure of MCP-3 was determined using multinuclear, multidimensional NMR spectroscopy with an expressed and 13C- and 15N-labeled protein. The MCP-3 has a typical chemokine fold including 3 anti-parallel -sheets, and a C-terminal helix, but it exists as a monomer in solution under the conditions where the structure was determined (2 mM, pH 5.1 at 30°C). Based on the structure and the amino acid sequence compared to other chemokines we propose that Ile20 and Leu25 in MCP-3 play key roles in the formation of N-loop (residues between the 2nd cysteine and the 1 sheet) which has been implicated as a determinant of chemokine specificity. Additional receptor binding surface is supplied by the 40s loop (residues between the 2 and the 3 sheet) and the binding interface of the acidic N-terminal region of chemokine receptor to MCP-3 would resemble the dimerization interface of CC type dimer.