Malay, Ali D. and Miyazaki, Naoyuki and Biela, Artur and Chakraborti, Soumyananda and Majsterkiewicz, Karolina and Stupka, Izabela and Kaplan, Craig S. and Kowalczyk, Agnieszka and Piette, Bernard M. A. G. and Hochberg, Georg K. A. and Wu, Di and Wrobel, Tomasz P. and Fineberg, Adam and Kushwah, Manish S. and Kelemen, Mitja and Vavpetič, Primož and Pelicon, Primož and Kukura, Philipp and Benesch, Justin L. P. and Iwasaki, Kenji and Heddle, Jonathan G. (2019) 'An ultra-stable gold-coordinated protein cage displaying reversible assembly.', Nature., 569 . pp. 438-442.
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.
|Full text:||(AM) Accepted Manuscript|
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|Publisher Web site:||https://doi.org/10.1038/s41586-019-1185-4|
|Publisher statement:||© 2019 Springer Nature Publishing AG.|
|Date accepted:||08 April 2019|
|Date deposited:||09 May 2019|
|Date of first online publication:||08 May 2019|
|Date first made open access:||08 November 2019|
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