A Superprotein Triangle Driven by Nickel(II) Coordination: Exploiting Non-Natural Metal Ligands in Protein Self-Assembly

We previously devised a strategy (metal-directed protein self-assembly, MDPSA) that utilizes the simultaneous stability, lability, and directionality of metal−ligand bonds to drive protein−protein interactions. Here we show that both the structural and functional scopes of MDPSA can be broadened by incorporation of non-natural metal-chelating ligands onto protein surfaces. A cytochrome cb562 variant, MBP-Phen1, which features a covalently attached phenanthroline (Phen) group on its surface, self-assembles into an unusual triangular architecture (Ni3:MBP-Phen13) upon binding Ni as a result of specific Phen−protein interactions. The crystal structure of Ni3:MBP-Phen13 reveals that the Phen group is buried in a small pocket on the protein surface, which results in an unsaturated Ni coordination environment.