National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM105691
米国
引用
ジャーナル: Commun Biol / 年: 2021 タイトル: Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces. 著者: Jazmine P Hallinan / Lindsey A Doyle / Betty W Shen / Mesfin M Gewe / Brittany Takushi / Madison A Kennedy / Della Friend / James M Roberts / Philip Bradley / Barry L Stoddard / 要旨: 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 ...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.