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Metal‐Templated Design of Chemically Switchable Protein Assemblies with High‐Affinity Coordination Sites
Author(s) -
Kakkis Albert,
Gag Derek,
Esselborn Julian,
Britt R. David,
Tezcan F. Akif
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202009226
Subject(s) - trimer , chemistry , metal , monomer , crystallography , protein design , structural motif , protein quaternary structure , protein structure , combinatorial chemistry , dimer , organic chemistry , protein subunit , biochemistry , gene , polymer
To mimic a hypothetical pathway for protein evolution, we previously tailored a monomeric protein (cyt cb 5 62 ) 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 cb 562 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.