Accurate and sensitive interactome profiling using a quantitative protein-fragment complementation assay

Cell Rep Methods. 2024 Oct 21;4(10):100880. doi: 10.1016/j.crmeth.2024.100880.

Abstract

An accurate description of protein-protein interaction (PPI) networks is key to understanding the molecular mechanisms underlying cellular systems. Here, we constructed genome-wide libraries of yeast strains to systematically probe protein-protein interactions using NanoLuc Binary Technology (NanoBiT), a quantitative protein-fragment complementation assay (PCA) based on the NanoLuc luciferase. By investigating an array of well-documented PPIs as well as the interactome of four proteins with varying levels of characterization-including the well-studied nonsense-mediated mRNA decay (NMD) regulator Upf1 and the SCF complex subunits Cdc53 and Met30-we demonstrate that ratiometric NanoBiT measurements enable highly precise and sensitive mapping of PPIs. This work provides a foundation for employing NanoBiT in the assembly of more comprehensive and accurate protein interaction maps as well as in their functional investigation.

Keywords: CP: Systems biology; Cdc53; Irc20; Met30; Nam7; NanoBiT; Saccharomyces cerevisiae; Upf1; budding yeast; interactome; protein-protein interaction.

MeSH terms

  • Luciferases / genetics
  • Luciferases / metabolism
  • Protein Interaction Mapping* / methods
  • Protein Interaction Maps
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • Luciferases