Engineering protein assemblies with allosteric control via monomer fold-switching

Luis A. Campos, Rajendra Sharma, Sara Alvira, Federico M. Ruiz, Beatriz Ibarra-Molero, Mourad Sadqi, Carlos Alfonso, Germán Rivas, Jose M. Sanchez-Ruiz, Antonio Romero Garrido, José M. Valpuesta and Victor Muñoz ()
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Luis A. Campos: Centro Nacional de Biotecnología (CNB-CSIC)
Rajendra Sharma: Centro Nacional de Biotecnología (CNB-CSIC)
Sara Alvira: Centro Nacional de Biotecnología (CNB-CSIC)
Federico M. Ruiz: Centro de Investigaciones Biológicas (CIB-CSIC)
Beatriz Ibarra-Molero: Universidad de Granada
Mourad Sadqi: University of California
Carlos Alfonso: Centro de Investigaciones Biológicas (CIB-CSIC)
Germán Rivas: Centro de Investigaciones Biológicas (CIB-CSIC)
Jose M. Sanchez-Ruiz: Universidad de Granada
Antonio Romero Garrido: Centro de Investigaciones Biológicas (CIB-CSIC)
José M. Valpuesta: Centro Nacional de Biotecnología (CNB-CSIC)
Victor Muñoz: Centro Nacional de Biotecnología (CNB-CSIC)

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract The macromolecular machines of life use allosteric control to self-assemble, dissociate and change shape in response to signals. Despite enormous interest, the design of nanoscale allosteric assemblies has proven tremendously challenging. Here we present a proof of concept of allosteric assembly in which an engineered fold switch on the protein monomer triggers or blocks assembly. Our design is based on the hyper-stable, naturally monomeric protein CI2, a paradigm of simple two-state folding, and the toroidal arrangement with 6-fold symmetry that it only adopts in crystalline form. We engineer CI2 to enable a switch between the native and an alternate, latent fold that self-assembles onto hexagonal toroidal particles by exposing a favorable inter-monomer interface. The assembly is controlled on demand via the competing effects of temperature and a designed short peptide. These findings unveil a remarkable potential for structural metamorphosis in proteins and demonstrate key principles for engineering protein-based nanomachinery.

Date: 2019
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DOI: 10.1038/s41467-019-13686-1

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