Engineering protein assemblies with allosteric control via monomer fold-switching

Luis Campos, Rajendra Sharma, Sara Alvira de Celis, Federico Ruiz, Beatriz Ibarra-Molero, Mourad Sadqi, Carlos Alfonso, Germán Rivas, Jose Sanchez-Ruiz, Antonio Romero Garrido, José Valpuesta, Victor Muñoz

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)
54 Downloads (Pure)


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.
Original languageEnglish
Article number5703 (2019)
Number of pages14
JournalNature Communications
Publication statusPublished - 13 Dec 2019


  • Computational biophysics
  • Molecular engineering
  • Nanobiotechnology
  • Protein folding
  • Structural biology


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