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

Angew Chem Int Ed Engl. 2020 Dec 1;59(49):21940-21944. doi: 10.1002/anie.202009226. Epub 2020 Sep 28.

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.

Keywords: bioinorganic chemistry; metalloproteins; protein design; protein structures; supramolecular chemistry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Hydrophobic and Hydrophilic Interactions
  • Metalloproteins / chemical synthesis*
  • Metalloproteins / chemistry
  • Metals, Heavy / chemistry*
  • Models, Molecular

Substances

  • Metalloproteins
  • Metals, Heavy