Integrating carbon nanoparticles (CNPs) with proteins to form hybrid functional assemblies is an innovative research area with great promise for medical, nanotechnology, and materials science. The comprehension of CNP-protein interactions requires the still-missing identification and characterization of the 'binding pocket' for the CNPs. Here, using Lysozyme and C 60 as model systems and NMR chemical shift perturbation analysis, a protein-CNP binding pocket is identified unambiguously in solution and the effect of the binding, at the level of the single amino acid, is characterized by a variety of experimental and computational approaches. Lysozyme forms a stoichiometric 1:1 adduct with C 60 that it is dispersed monomolecularly in water. Lysozyme maintains its tridimensional structure upon interaction with C 60 and only a few identified residues are perturbed. The C 60 recognition is highly specific and localized in a well-defined pocket.