An ultra-stable gold-coordinated protein cage displaying reversible assembly - PubMed (original) (raw)

. 2019 May;569(7756):438-442.

doi: 10.1038/s41586-019-1185-4. Epub 2019 May 8.

Naoyuki Miyazaki 3, Artur Biela 4 5, Soumyananda Chakraborti 4, Karolina Majsterkiewicz 4 6, Izabela Stupka 4 6, Craig S Kaplan 7, Agnieszka Kowalczyk 4 8, Bernard M A G Piette 9, Georg K A Hochberg 10 11, Di Wu 10, Tomasz P Wrobel 12, Adam Fineberg 10, Manish S Kushwah 10, Mitja Kelemen 13 14, Primož Vavpetič 13, Primož Pelicon 13, Philipp Kukura 10, Justin L P Benesch 10, Kenji Iwasaki 3 15, Jonathan G Heddle 16 17

Affiliations

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

Ali D Malay et al. Nature. 2019 May.

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.

PubMed Disclaimer

Comment in

Similar articles

Cited by

References

    1. Aumiller, W. M., Uchida, M. & Douglas, T. Protein cage assembly across multiple length scales. Chem. Soc. Rev. 47, 3433–3469 (2018). - DOI
    1. Bale, J. B. et al. Accurate design of megadalton-scale two-component icosahedral protein complexes. Science 353, 389–394 (2016). - DOI
    1. Yeates, T. O. Geometric principles for designing highly symmetric self-assembling protein nanomaterials. Annu. Rev. Biophys. 46, 23–42 (2017). - DOI
    1. Padilla, J. E., Colovos, C. & Yeates, T. O. Nanohedra: using symmetry to design self assembling protein cages, layers, crystals, and filaments. Proc. Natl Acad. Sci. USA 98, 2217–2221 (2001). - DOI
    1. King, N. P. et al. Computational design of self-assembling protein nanomaterials with atomic level accuracy. Science 336, 1171–1174 (2012). - DOI

Publication types

MeSH terms

Substances

LinkOut - more resources