Metals at the Helm: Revolutionizing Protein Assembly and Applications

Abstract

Protein assembly is an essential process in biological systems, where proteins self‐assemble into complex structures with diverse functions. Inspired by the exquisite control over protein assembly in nature, scientists have been exploring ways to design and assemble protein structures with precise control over their topologies and functions. One promising approach for achieving this goal is through metal coordination, which utilizes metal‐binding motifs to mediate protein‐protein interactions and assemble protein complexes with controlled stoichiometry and geometry. Metal coordination provides a modular and tunable approach for protein assembly and de novo structure design, where the metal ion acts as a molecular glue that holds the protein subunits together in a specific orientation. Metal‐coordinated protein assemblies have shown great potential for developing functional metalloproteinase, novel biomaterials and integrated drug delivery systems. In this review, an overview of the recent advances in protein assemblies benefited from metal coordination is provided, focusing on various protein arrangements in different dimensions including protein oligomers, protein nanocage and higher‐order protein architectures. Moreover, the key metal‐binding motifs and strategies used to assemble protein structures with precise control over their properties are highlighted. The potential applications of metal‐mediated protein assemblies in biotechnology and biomedicine are also discussed.