Chemokine signaling is essential for inflammation. The chemokine receptor CCR1 is suggested to be a novel therapeutic target for anti-inflammatory therapy in pulmonary fibrosis. CCR1 shares common ligands with CCR2 and CCR5, and thus is involved in the occurrence of rheumatoid arthritis and multiple sclerosis. We previously searched for proteins that bind to the membrane proximal C-terminal region (Pro-C) of CCR1, by a yeast two-hybrid assay, and identified a cytoplasmic protein, R1-15. Furthermore, a Boyden chamber assay revealed that the cell migration activity was decreased when the expression of R1-15 was inhibited by siRNA. Therefore, R1-15 is apparently involved in CCR1-mediated intracellular signaling, and thus the control of R1-15 may be a treatment for chronic inflammatory diseases. The aim of this study is to elucidate the CCR1-binding mechanism of R1-15 and to develop candidate compounds that inhibit the R1-15–CCR1 interaction, based on the three-dimensional structures of R1-15 and CCR1. A ~13 kDa segment of R1-15 that bound to CCR1 Pro-C was identified by the yeast two-hybrid assay. A procedure for the expression and purification of the CCR1-binding segment was established, using an E. coli expression system. NMR and CD analyses revealed that the prepared CCR1-binding segment adopted an α-helical structure. In the 1H–15N HSQC NMR measurement for the CCR1-binding segment, the detected amide signals were broader than those expected from the molecular weight as a monomer, indicating that the CCR1-binding region of R1-15 formed aggregates. We are currently trying to identify the structural domain that exists without aggregation and is suitable for the structure analysis. The structural and functional study for the domain identification will be reported.