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Design of Protein Assemblies with Built-In Allosteric Control Based on Monomer Fold-Switching
- Source :
- Digital.CSIC: Repositorio Institucional del CSIC, Consejo Superior de Investigaciones Científicas (CSIC), Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2019
- Publisher :
- Springer Nature, 2019.
-
Abstract
- © The Author(s) 2019.<br />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.<br />This work was supported by the European Research Council (grant ERC-2012-ADG-323059 to V.M.) and by the PRODESTECH network funded through the CONSOLIDER program from the Spanish Government (grant CSD2009-00088). L.A.C. acknowledges support from Ministry of Economy and Competitiveness through grants BIO2016-78768-P and RYC-2013-13197. V.M. acknowledges additional support from the W.M. Keck Foundation and from the CREST Center for Cellular and Biomomolecular Machines (grant NSF-CREST-1547848). J.M.V. acknowledges additional support from Ministry of Economy and Competitiveness through grant BFU2016-75984. F.M.R. and A.R. thank the staff from the ALBA synchrotron (Spain) for assistance with the XALOC beamline. Structural data are deposited in the Protein Data Bank with accession codes 6QIY (X-ray CI2 classical geometry) and 6QIZ (X-ray CI2 domain swapped) and EMD-4568 (cryo-EM CI2eng assembly).
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC: Repositorio Institucional del CSIC, Consejo Superior de Investigaciones Científicas (CSIC), Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.dedup.wf.001..28dc33cca73443b382377d6f4bff7dc0