Protein-fragment complementation assays for large-scale analysis of protein-protein interactions

Biochem Soc Trans. 2021 Jun 30;49(3):1337-1348. doi: 10.1042/BST20201058.

Abstract

Protein-protein interactions (PPIs) orchestrate nearly all biological processes. They are also considered attractive drug targets for treating many human diseases, including cancers and neurodegenerative disorders. Protein-fragment complementation assays (PCAs) provide a direct and straightforward way to study PPIs in living cells or multicellular organisms. Importantly, PCAs can be used to detect the interaction of proteins expressed at endogenous levels in their native cellular environment. In this review, we present the principle of PCAs and discuss some of their advantages and limitations. We describe their application in large-scale experiments to investigate PPI networks and to screen or profile PPI targeting compounds.

Keywords: drug targets; high-throughput screening; large-scale; protein-fragment complementation assays; protein–protein interactions; proteome-wide analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Models, Molecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Protein Binding
  • Protein Domains
  • Protein Interaction Mapping / methods*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Proteome / chemistry
  • Proteome / metabolism
  • Proteomics / methods

Substances

  • Peptide Fragments
  • Peptides
  • Proteins
  • Proteome