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Title: Constructing protein polyhedra via orthogonal chemical interactions

Abstract

Many proteins exist naturally as symmetrical homooligomers or homopolymers. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design2–5. As synthesized by ribosomes, proteins are inherently asymmetric. Therefore, they must acquire multiple surface patches that selectively associate to generate the different symmetry elements needed to form higher-order architectures—a daunting task for protein design. Here we address this problem using an inorganic chemical approach, whereby multiple modes of protein–protein interactions and symmetry are simultaneously achieved by selective, ‘one-pot’ coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and zinc-binding motifs assembles through concurrent Fe 3+ and Zn 2+ coordination into discrete dodecameric and hexameric cages. Our cages closely resemble natural polyhedral protein architectures and are, to our knowledge, unique among designed systems in that they possess tightly packed shells devoid of large apertures. At the same time, they can assemble and disassemble in response to diverse stimuli, owing to their heterobimetallic construction on minimal interprotein-bonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomers] to [8 Fe:21 Zn:12 protomers], these protein cages represent some of the compositionally most complex protein assemblies—or inorganicmore » coordination complexes—obtained by design.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Univ. of California, San Diego, CA (United States)
Publication Date:
Research Org.:
Univ. of California, San Diego, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division
OSTI Identifier:
1594978
Grant/Contract Number:  
SC0003844
Resource Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; 59 BASIC BIOLOGICAL SCIENCES; 77 NANOSCIENCE AND NANOTECHNOLOGY

Citation Formats

Golub, Eyal, Subramanian, Rohit H., Esselborn, Julian, Alberstein, Robert G., Bailey, Jake B., Chiong, Jerika A., Yan, Xiaodong, Booth, Timothy, Baker, Timothy S., and Tezcan, F. Akif. Constructing protein polyhedra via orthogonal chemical interactions. United States: N. p., 2020. Web. doi:10.1038/s41586-019-1928-2.
Golub, Eyal, Subramanian, Rohit H., Esselborn, Julian, Alberstein, Robert G., Bailey, Jake B., Chiong, Jerika A., Yan, Xiaodong, Booth, Timothy, Baker, Timothy S., & Tezcan, F. Akif. Constructing protein polyhedra via orthogonal chemical interactions. United States. doi:10.1038/s41586-019-1928-2.
Golub, Eyal, Subramanian, Rohit H., Esselborn, Julian, Alberstein, Robert G., Bailey, Jake B., Chiong, Jerika A., Yan, Xiaodong, Booth, Timothy, Baker, Timothy S., and Tezcan, F. Akif. Wed . "Constructing protein polyhedra via orthogonal chemical interactions". United States. doi:10.1038/s41586-019-1928-2.
@article{osti_1594978,
title = {Constructing protein polyhedra via orthogonal chemical interactions},
author = {Golub, Eyal and Subramanian, Rohit H. and Esselborn, Julian and Alberstein, Robert G. and Bailey, Jake B. and Chiong, Jerika A. and Yan, Xiaodong and Booth, Timothy and Baker, Timothy S. and Tezcan, F. Akif},
abstractNote = {Many proteins exist naturally as symmetrical homooligomers or homopolymers. The emergent structural and functional properties of such protein assemblies have inspired extensive efforts in biomolecular design2–5. As synthesized by ribosomes, proteins are inherently asymmetric. Therefore, they must acquire multiple surface patches that selectively associate to generate the different symmetry elements needed to form higher-order architectures—a daunting task for protein design. Here we address this problem using an inorganic chemical approach, whereby multiple modes of protein–protein interactions and symmetry are simultaneously achieved by selective, ‘one-pot’ coordination of soft and hard metal ions. We show that a monomeric protein (protomer) appropriately modified with biologically inspired hydroxamate groups and zinc-binding motifs assembles through concurrent Fe3+ and Zn2+ coordination into discrete dodecameric and hexameric cages. Our cages closely resemble natural polyhedral protein architectures and are, to our knowledge, unique among designed systems in that they possess tightly packed shells devoid of large apertures. At the same time, they can assemble and disassemble in response to diverse stimuli, owing to their heterobimetallic construction on minimal interprotein-bonding footprints. With stoichiometries ranging from [2 Fe:9 Zn:6 protomers] to [8 Fe:21 Zn:12 protomers], these protein cages represent some of the compositionally most complex protein assemblies—or inorganic coordination complexes—obtained by design.},
doi = {10.1038/s41586-019-1928-2},
journal = {Nature (London)},
number = ,
volume = ,
place = {United States},
year = {2020},
month = {1}
}

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