Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces.
Commun Biol
; 4(1): 1240, 2021 10 29.
Article
in English
| MEDLINE | ID: covidwho-1493232
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Protein Engineering
/
Proteins
/
Tandem Repeat Sequences
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Commun Biol
Year:
2021
Document Type:
Article
Affiliation country:
S42003-021-02766-y
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