Open AccessEngineering and functionalization of large circular tandem repeat protein nanoparticles
Author(s) -
Colin Correnti,
J.P. Hallinan,
Lindsey Doyle,
Raymond O. Ruff,
Carla A. Jaeger-Ruckstuhl,
Yuexin Xu,
Betty Shen,
Amanda Qu,
Caley Polkinghorn,
Della Friend,
Ashok D. Bandaranayake,
Stanley R. Riddell,
Brett K. Kaiser,
Barry Stoddard,
Philip Bradley
Publication year - 2020
Publication title -
nature structural and molecular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.448
H-Index - 270
eISSN - 1545-9993
pISSN - 1545-9985
DOI - 10.1038/s41594-020-0397-5
Subject(s) - avidity , protein engineering , tandem , protein subunit , protein design , computational biology , protein–protein interaction , protein structure , nanotechnology , chemistry , biology , biophysics , microbiology and biotechnology , materials science , biochemistry , genetics , enzyme , antibody , gene , composite material
Protein engineering has enabled the design of molecular scaffolds that display a wide variety of sizes, shapes, symmetries and subunit compositions. Symmetric protein-based nanoparticles that display multiple protein domains can exhibit enhanced functional properties due to increased avidity and improved solution behavior and stability. Here we describe the creation and characterization of a computationally designed circular tandem repeat protein (cTRP) composed of 24 identical repeated motifs, which can display a variety of functional protein domains (cargo) at defined positions around its periphery. We demonstrate that cTRP nanoparticles can self-assemble from smaller individual subunits, can be produced from prokaryotic and human expression platforms, can employ a variety of cargo attachment strategies and can be used for applications (such as T-cell culture and expansion) requiring high-avidity molecular interactions on the cell surface.