Self-assembly and regulation of protein cages from pre-organised coiled-coil modules
Abstract
Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. CCPO folds are defined by the sequential order of concatenated orthogonal coiled-coil (CC) dimer-forming peptides, where a single-chain protein is programmed to fold into a polyhedral cage. Self-assembly of CC-based nanostructures from several chains, similarly as in DNA nanotechnology, could facilitate the design of more complex assemblies and the introduction of functionalities. Here, we show the design of a de novo triangular bipyramid fold comprising 18 CC-forming segments and define the strategy for the two-chain self-assembly of the bipyramidal cage from asymmetric and pseudo-symmetric pre-organised structural modules. In addition, by introducing a protease cleavage site and masking the interfacial CC-forming segments in the two-chain bipyramidal cage, we devise a proteolysis-mediated conformational switch. This strategy could be extended to other modular protein folds, facilitating the construction of dynamic multi-chain CC-based complexes.
- Authors:
-
[1];
[2];
[4];
[5];
[1]
- National Inst. of Chemistry, Ljubljana (Slovenia). Dept. of Synthetic Biology and Immunology; EN-FIST Centre of Excellence, Ljubljana (Slovenia)
- National Inst. of Chemistry, Ljubljana (Slovenia). Dept. of Synthetic Biology and Immunology
- Univ. of Parma (Italy). Life Sciences and Environmental Sustainability. Dept. of Chemistry
- Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)
- Consejo Superior de Investigaciones Cientificas (CSIC), Madrid (Spain). Centro Nacional de Biotecnología (CNB-CSIC)
- Publication Date:
- Sponsoring Org.:
- USDOE Office of Science (SC); Slovenian Research Agency; European Research Council (ERC); European Commission (EC); European Union (EU)
- OSTI Identifier:
- 1816455
- Grant/Contract Number:
- AC02-05CH11231; P4-0176; J1-9173; J3-7034; N4-0080; 820699; 653706; P30 GM124169; S10OD018483
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 12; Journal Issue: 1; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; nanostructures; protein design; SAXS; synthetic biology
Citation Formats
Lapenta, Fabio, Aupič, Jana, Vezzoli, Marco, Strmšek, Žiga, Da Vela, Stefano, Svergun, Dmitri I., Carazo, José María, Melero, Roberto, and Jerala, Roman. Self-assembly and regulation of protein cages from pre-organised coiled-coil modules. United States: N. p., 2021.
Web. doi:10.1038/s41467-021-21184-6.
Lapenta, Fabio, Aupič, Jana, Vezzoli, Marco, Strmšek, Žiga, Da Vela, Stefano, Svergun, Dmitri I., Carazo, José María, Melero, Roberto, & Jerala, Roman. Self-assembly and regulation of protein cages from pre-organised coiled-coil modules. United States. https://doi.org/10.1038/s41467-021-21184-6
Lapenta, Fabio, Aupič, Jana, Vezzoli, Marco, Strmšek, Žiga, Da Vela, Stefano, Svergun, Dmitri I., Carazo, José María, Melero, Roberto, and Jerala, Roman. Thu .
"Self-assembly and regulation of protein cages from pre-organised coiled-coil modules". United States. https://doi.org/10.1038/s41467-021-21184-6. https://www.osti.gov/servlets/purl/1816455.
@article{osti_1816455,
title = {Self-assembly and regulation of protein cages from pre-organised coiled-coil modules},
author = {Lapenta, Fabio and Aupič, Jana and Vezzoli, Marco and Strmšek, Žiga and Da Vela, Stefano and Svergun, Dmitri I. and Carazo, José María and Melero, Roberto and Jerala, Roman},
abstractNote = {Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. CCPO folds are defined by the sequential order of concatenated orthogonal coiled-coil (CC) dimer-forming peptides, where a single-chain protein is programmed to fold into a polyhedral cage. Self-assembly of CC-based nanostructures from several chains, similarly as in DNA nanotechnology, could facilitate the design of more complex assemblies and the introduction of functionalities. Here, we show the design of a de novo triangular bipyramid fold comprising 18 CC-forming segments and define the strategy for the two-chain self-assembly of the bipyramidal cage from asymmetric and pseudo-symmetric pre-organised structural modules. In addition, by introducing a protease cleavage site and masking the interfacial CC-forming segments in the two-chain bipyramidal cage, we devise a proteolysis-mediated conformational switch. This strategy could be extended to other modular protein folds, facilitating the construction of dynamic multi-chain CC-based complexes.},
doi = {10.1038/s41467-021-21184-6},
journal = {Nature Communications},
number = 1,
volume = 12,
place = {United States},
year = {Thu Feb 11 00:00:00 EST 2021},
month = {Thu Feb 11 00:00:00 EST 2021}
}
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