Constructing protein polyhedra via orthogonal chemical interactions

Journal Article · 22 January 2020 · Nature (London)

DOI: https://doi.org/10.1038/s41586-019-1928-2 · OSTI ID:1594978

Golub, Eyal ^[1]; Subramanian, Rohit H. ^[2]; Esselborn, Julian ^[2]; Alberstein, Robert G. ^[2]; Bailey, Jake B. ^[2]; Chiong, Jerika A. ^[2]; Yan, Xiaodong ^[2]; Booth, Timothy ^[2]; Baker, Timothy S. ^[2]; Tezcan, F. Akif ^[2]

---

1. Univ. of California, San Diego, CA (United States); University of California, San Diego
2. Univ. of California, San Diego, CA (United States)

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.

• Research Organization: Univ. of California, San Diego, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division
• Grant/Contract Number: SC0003844
• OSTI ID: 1594978
• Journal Information: Nature (London), Journal Name: Nature (London) Vol. 578; ISSN 0028-0836
• Publisher: Nature Publishing GroupCopyright Statement
• Country of Publication: United States
• Language: English