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The recruitment and activation of neutrophils are essential steps in the immune response. These actions are triggered by the release of chemokines that direct the neutrophils to the affected site where they combat inflammation and kill bacteria. Here we utilize the example of chemokine interleukin-8 (IL-8) interacting with the G protein-coupled receptor CXCR1 to demonstrate the use of NMR spectroscopy to describe key protein components of the immune system in terms of their structures, dynamics, and molecular interactions within membrane bilayers. The IL-8 binding site in CXCR1 is often envisioned as being comprised of two distinct parts of the receptor: Binding Site-I is associated with the receptor's flexible N-terminal domain and Binding Site-II is associated with the second and third extracellular loops near the middle of the 350-residue polypeptide. We also describe how the dynamics of 1TM-CXCR1, a CXCR1 construct consisting of the N-terminal residues 1–72, change upon interaction with IL-8. Most of the residues in the flexible N-terminal domain undergo chemical shift perturbations; residues 1–37 also undergo changes in dynamics upon binding the chemokine. Little evidence of changes was observed in residues located more distal to the N-terminus in the first transmembrane helix of the receptor. These interpretations are possible because of the foundation laid by previous results, which determined the three-dimensional structures of IL-8 and CXCR1, characterized the global and local dynamics of both proteins, and described how their structures and dynamics are affected by their interactions.

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