Tadej Satler (Author), San Hadži (Author), Roman Jerala (Author)

Abstract

Coiled-coil protein origami (CCPO) uses modular coiled-coil building blocks and topological principles to design polyhedral structures distinct from those of natural globular proteins. While the CCPO strategy has proven successful in designing diverse protein topologies, no high-resolution structural information has been available about these novel protein folds. Here we report the crystal structure of a single-chain CCPO in the shape of a triangle. While neither cyclization nor the addition of nanobodies enabled crystallization, it was ultimately facilitated by the inclusion of a GCN$_2$ homodimer. Triangle edges are formed by the orthogonal parallel coiled-coil dimers P1:P2, P3:P4, and GCN$_2$ connected by short linkers. A triangle has a large central cavity and is additionally stabilized by side-chain interactions between neighboring segments at each vertex. The crystal lattice is densely packed and stabilized by a large number of contacts between triangles. Interestingly, the polypeptide chain folds into a trefoil-type protein knot topology, and AlphaFold2 fails to predict the correct fold. The structure validates the modular CC-based protein design strategy, providing molecular insight underlying CCPO stabilization and new opportunities for the design.

Keywords

biokemija;proteinski origami;obvite vijačnice;CCPO;DNK;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: KI - National Institute of Chemistry
Publisher: American Chemical Society
UDC: 577
COBISS: 169812995 Link will open in a new window
ISSN: 1520-5126
Views: 13
Downloads: 4
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Other data

Secondary language: Slovenian
Secondary keywords: biokemija;proteinski origami;obvite vijačnice;CCPO;DNK;
Type (COBISS): Article
Source comment: Nasl. z nasl. zaslona; Opis vira z dne 25. 10. 2023;
Pages: str. 16995–17000
Volume: ǂVol. ǂ145
Issue: ǂiss. ǂ31
Chronology: Aug. 9, 2023
DOI: 10.1021/jacs.3c05531
ID: 21439512