A general method for chemogenetic control of peptide function

Jiaqi Shen, Lequn Geng, Xingyu Li, Catherine Emery, Kayla Kroning, Gwendolyn Shingles, Kerry Lee, Matthias Heyden, Peng Li, Wenjing Wang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Natural or engineered peptides serve important biological functions. A general approach to achieve chemical-dependent activation of short peptides will be valuable for spatial and temporal control of cellular processes. Here we present a pair of chemically activated protein domains (CAPs) for controlling the accessibility of both the N- and C-terminal portion of a peptide. CAPs were developed through directed evolution of an FK506-binding protein. By fusing a peptide to one or both CAPs, the function of the peptide is blocked until a small molecule displaces them from the FK506-binding protein ligand-binding site. We demonstrate that CAPs are generally applicable to a range of short peptides, including a protease cleavage site, a dimerization-inducing heptapeptide, a nuclear localization signal peptide, and an opioid peptide, with a chemical dependence up to 156-fold. We show that the CAPs system can be utilized in cell cultures and multiple organs in living animals.

Original languageEnglish (US)
Pages (from-to)112-122
Number of pages11
JournalNature Methods
Volume20
Issue number1
DOIs
StatePublished - Jan 2023

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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