8P4Y

Coiled-coil protein origami triangle

Summary for 8P4Y

• Entry DOI: 10.2210/pdb8p4y/pdb
• Descriptor: Protein origami triangle, GLYCEROL (3 entities in total)
• Functional Keywords: coiled-coil, protein origami, designed protein, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 24496.32

Authors

Satler, T.,Hadzi, S.,Jerala, R. (deposition date: 2023-05-23, release date: 2023-08-02, Last modification date: 2023-08-23)

Primary citation

Satler, T.,Hadzi, S.,Jerala, R.
Crystal Structure of de Novo Designed Coiled-Coil Protein Origami Triangle.
J.Am.Chem.Soc., 145:16995-17000, 2023

PubMed 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 homodimer. Triangle edges are formed by the orthogonal parallel coiled-coil dimers P1:P2, P3:P4, and GCN 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.

PubMed: 37486611
DOI: 10.1021/jacs.3c05531

Experimental method

X-RAY DIFFRACTION (2.052 Å)