Metal‐Templated Design of Chemically Switchable Protein Assemblies with High‐Affinity Coordination Sites

Abstract

AbstractTo mimic a hypothetical pathway for protein evolution, we previously tailored a monomeric protein (cyt cb562) for metal‐mediated self‐assembly, followed by re‐design of the resulting oligomers for enhanced stability and metal‐based functions. We show that a single hydrophobic mutation on the cyt cb562 surface drastically alters the outcome of metal‐directed oligomerization to yield a new trimeric architecture, (TriCyt1)3. This nascent trimer was redesigned into second and third‐generation variants (TriCyt2)3 and (TriCyt3)3 with increased structural stability and preorganization for metal coordination. The three TriCyt variants combined furnish a unique platform to 1) provide tunable coupling between protein quaternary structure and metal coordination, 2) enable the construction of metal/pH‐switchable protein oligomerization motifs, and 3) generate a robust metal coordination site that can coordinate all mid‐to‐late first‐row transition‐metal ions with high affinity.