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

ABSTRACT: To 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.

SUBMITTER: Kakkis A

PROVIDER: S-EPMC7983065 | biostudies-literature |

REPOSITORIES: biostudies-literature

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