Hierarchical Self-Assembly of a Supramolecular Protein-Metal Cage Encapsulating a Polyoxometalate Guest

Hierarchical self-assembly of hybrid bioinorganic structures is a challenging task which requires specific and tailored interactions. Here we report a supramolecular assembly formed between the six-bladed symmetrical designer protein Pizza6-S (Pizza6) and the {K3Cu3(NO3)[A-α-PW9O34]2} (Cu3) polyoxometalate (POM). The crystal structure (1.8 Å resolution) revealed that the Cu3 dissociated and reassembled with the protein to form a novel POM-protein cage. In this hybrid assembly, six CuII ions link two Pizza6 molecules in a controlled way by binding to the six symmetrically equivalent histidine side chains. Such coordination results in the formation of a “bioinorganic cage” in which a lacunary [A-α-PW9O34]9– (PW9) anion is tightly encapsulated via coordination to CuII ions and hydrogen bonding with protein side chains. Further spectroscopic characterization of the Pizza6/Cu3 solution suggests that dissociation of Cu3 is facilitated by the synergetic effect of six histidine residues which have high affinity toward Cu(II) ions, resulting in the formation of the hierarchical supramolecular assembly.