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Molecular machines based on coiled-coil protein origami

Objective

Proteins are the most versatile and complex smart nanomaterials, forming molecular machines and performing numerous functions from structure building, recognition, catalysis to locomotion. Nature however explored only a tiny fraction of possible protein sequences and structures. Design of proteins with new, in nature unseen shapes and features, offers high rewards for medicine, technology and science. In 2013 my group pioneered the design of a new type of modular coiled-coil protein origami (CCPO) folds. This type of de novo designed proteins are defined by the sequence of coiled-coil (CC) dimer-forming modules that are concatenated by flexible linkers into a single polypeptide chain that self-assembles into a polyhedral cage based on pairwise CC interactions. This is in contrast to naturally evolved proteins where their fold is defined by a compact hydrophobic core. We recently demonstrated the robustness of this strategy by the largest de novo designed single chain protein, construction of tetrahedral, pyramid, trigonal prism and bipyramid cages that self-assemble in vivo.
This proposal builds on unique advantages of CCPOs and represents a new frontier of this branch of protein design science. I propose to introduce functional domains into selected positions of CCPO cages, implement new types of building modules that will enable regulated CCPO assembly and disassembly, test new strategies of caging and release of cargo molecules for targeted delivery, design knotted and crosslinked protein cages and introduce toehold displacement for the regulated structural rearrangement of CCPOs required for designed molecular machines, which will be demonstrated on protein nanotweezers. Technology for the positional combinatorial library-based single pot assembly of CCPO genes will provide high throughput of CCPO variants. Project will result in new methodology, understanding of potentials of CCPOs for designed molecular machines and in demonstration of different applications.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-ADG - Advanced Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2017-ADG

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Host institution

KEMIJSKI INSTITUT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 362 838,75
Address
HAJDRIHOVA 19
1000 Ljubljana
Slovenia

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Region
Slovenija Zahodna Slovenija Osrednjeslovenska
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 362 838,75

Beneficiaries (2)

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