@misc{10481/58553,
year = {2019},
url = {http://hdl.handle.net/10481/58553},
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.},
organization = {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).},
publisher = {Springer Nature},
title = {Engineering protein assemblies with allosteric control via monomer fold-switching},
doi = {10.1038/s41467-019-13686-1},
author = {Campos, Luis and Sadqi, Mourad and Muñoz, Victor},
}