Biological receptors such as enzymes are highly flexible and alter their conformation to fit target substrates. Synthetic supramolecular hosts such as coordination cages also exhibit some ability to adapt their cavity shape and size in response to guest molecules, due to the dynamic nature of the linkages that hold them together. Here we report the preparation of a new trigonal-prismatic coordination cage that forms selectively, incorporating two different ligands. The cage exhibits up to four diastereomeric configurations, differing in the ‘portrait’ or ‘landscape’ orientation of tetratopic pyrene-based ligands on its rectangular faces. Three diastereomeric forms of the cage have been structurally characterised, and NMR spectroscopy confirmed the formation of a mixture of diastereomers in solution. Although the cage panels are rigid, the different orientations that each panel can adopt enables the cage cavity to dynamically adapt to optimize the binding of guests including elongated adamantane derivatives and toxic organochlorine pesticides.