6XR2

Computationally designed right-handed alpha/alpha homotrimeric toroid with 3 repeats per subunit

Summary for 6XR2

• Entry DOI: 10.2210/pdb6xr2/pdb
• Descriptor: dTor_3x57R (2 entities in total)
• Functional Keywords: computationally designed, de novo, toroid, helix-turn-helix, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 6
• Total formula weight: 113709.04

Authors

Hallinan, J.P.,Doyle, L.,Bradley, P.,Stoddard, B.L. (deposition date: 2020-07-10, release date: 2021-07-14, Last modification date: 2024-05-22)

Primary citation

Hallinan, J.P.,Doyle, L.A.,Shen, B.W.,Gewe, M.M.,Takushi, B.,Kennedy, M.A.,Friend, D.,Roberts, J.M.,Bradley, P.,Stoddard, B.L.
Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces.
Commun Biol, 4:1240-1240, 2021

PubMed Abstract: Circular tandem repeat proteins ('cTRPs') are de novo designed protein scaffolds (in this and prior studies, based on antiparallel two-helix bundles) that contain repeated protein sequences and structural motifs and form closed circular structures. They can display significant stability and solubility, a wide range of sizes, and are useful as protein display particles for biotechnology applications. However, cTRPs also demonstrate inefficient self-assembly from smaller subunits. In this study, we describe a new generation of cTRPs, with longer repeats and increased interaction surfaces, which enhanced the self-assembly of two significantly different sizes of homotrimeric constructs. Finally, we demonstrated functionalization of these constructs with (1) a hexameric array of peptide-binding SH2 domains, and (2) a trimeric array of anti-SARS CoV-2 VHH domains. The latter proved capable of sub-nanomolar binding affinities towards the viral receptor binding domain and potent viral neutralization function.

PubMed: 34716407
DOI: 10.1038/s42003-021-02766-y

Experimental method

X-RAY DIFFRACTION (3.2 Å)