An ultra-stable gold-coordinated protein cage displaying reversible assembly

Malay, Ali D.; Miyazaki, Naoyuki; Biela, Artur; Chakraborti, Soumyananda; Majsterkiewicz, Karolina; Stupka, Izabela; Kaplan, Craig S.; Kowalczyk, Agnieszka; Piette, Bernard M.A.G.; Hochberg, Georg K.A.; Wu, Di; Wrobel, Tomasz P.; Fineberg, Adam; Kushwah, Manish S.; Kelemen, Mitja; Vavpetič, Primož; Pelicon, Primož; Kukura, Philipp; Benesch, Justin L.P.; Iwasaki, Kenji; Heddle, Jonathan G.

Abstract

Symmetrical protein cages have evolved to fulfil diverse roles in nature, including compartmentalization and cargo delivery1, and have inspired synthetic biologists to create novel protein assemblies via the precise manipulation of protein–protein interfaces. Despite the impressive array of protein cages produced in the laboratory, the design of inducible assemblies remains challenging2,3. Here we demonstrate an ultra-stable artificial protein cage, the assembly and disassembly of which can be controlled by metal coordination at the protein–protein interfaces. The addition of a gold (i)-triphenylphosphine compound to a cysteine-substituted, 11-mer protein ring triggers supramolecular self-assembly, which generates monodisperse cage structures with masses greater than 2 MDa. The geometry of these structures is based on the Archimedean snub cube and is, to our knowledge, unprecedented. Cryo-electron microscopy confirms that the assemblies are held together by 120 S–Aui–S staples between the protein oligomers, and exist in two chiral forms. The cage shows extreme chemical and thermal stability, yet it readily disassembles upon exposure to reducing agents. As well as gold, mercury(ii) is also found to enable formation of the protein cage. This work establishes an approach for linking protein components into robust, higher-order structures, and expands the design space available for supramolecular assemblies to include previously unexplored geometries.

Citation

Malay, A. D., Miyazaki, N., Biela, A., Chakraborti, S., Majsterkiewicz, K., Stupka, I., …Heddle, J. G. (2019). An ultra-stable gold-coordinated protein cage displaying reversible assembly. Nature, 569, 438-442. https://doi.org/10.1038/s41586-019-1185-4

• Journal Article Type: Article
• Acceptance Date: Apr 8, 2019
• Online Publication Date: May 8, 2019
• Publication Date: May 8, 2019
• Deposit Date: May 9, 2019
• Publicly Available Date: Nov 8, 2019
• Journal: Nature
• Print ISSN: 0028-0836
• Electronic ISSN: 1476-4687
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 569
• Pages: 438-442
• DOI: https://doi.org/10.1038/s41586-019-1185-4
• Public URL: https://durham-repository.worktribe.com/output/1330924