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

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 cb5...

Full description

Saved in:
Bibliographic Details
Published inAngewandte Chemie International Edition Vol. 59; no. 49; pp. 21940 - 21944
Main Authors Kakkis, Albert, Gagnon, Derek, Esselborn, Julian, Britt, R. David, Tezcan, F. Akif
Format Journal Article
LanguageEnglish
Published 2230 Support Wiley 01.12.2020
Wiley Subscription Services, Inc
EditionInternational ed. in English
Subjects
Affinity
bioinorganic chemistry
Chemistry and Materials (General)
Coordination
Hydrophobic and Hydrophilic Interactions
Hydrophobicity
Metal ions
metalloproteins
Metalloproteins - chemical synthesis
Metalloproteins - chemistry
Metals
Metals, Heavy - chemistry
Models, Molecular
Mutation
Oligomerization
Oligomers
protein design
Protein structure
protein structures
Proteins
Quaternary structure
Structural stability
supramolecular chemistry
Trimers
protein structures
protein design
supramolecular chemistry
metalloproteins
bioinorganic chemistry
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:2230 Support
2230
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202009226