Homotropic and heterotropic allosteric interactions are important mechanisms that regulate protein function. These mechanisms depend on the ability of oligomeric protein complexes to adopt different conformations and to transmit conformation-linked signals from one subunit of the complex to the neighboring ones. An important step in understanding the regulation of protein function is to identify and characterize the conformations available to the protein complex. This task becomes increasingly challenging with increasing numbers of interacting binding sites. However, a large number of interacting binding sites allows for high homotropic interactions (cooperativity) and thus represents the most interesting case. Examples of very large, cooperative protein complexes are the giant hexagonal bilayer hemoglobins of annelid worms that contain 144 oxygen-binding sites. Moreover, these proteins show strict hierarchy in structure. In order to understand the interaction of various ligands such as oxygen, CO, or nitric oxide (NO), the principle binding behavior of these protein complexes has to be understood. For the hemoglobins of two species, the hierarchical structure is shown to have functional implications. By employing simultaneous analysis of several oxygen-binding curves, it could be shown that the nested MWC model provides a good description of the functional data. A strategy for the experimental setup and data analysis is suggested that allows for a reduction in the number of free parameters. Possible advantages of a hierarchical cooperative model compared to a linear extension of the MWC model are discussed.