Split-miniSOG for Spatially Detecting Intracellular Protein-Protein Interactions by Correlated Light and Electron Microscopy

Cell Chem Biol. 2019 Oct 17;26(10):1407-1416.e5. doi: 10.1016/j.chembiol.2019.07.007. Epub 2019 Aug 1.


A protein-fragment complementation assay (PCA) for detecting and localizing intracellular protein-protein interactions (PPIs) was built by bisection of miniSOG, a fluorescent flavoprotein derived from the light, oxygen, voltage (LOV)-2 domain of Arabidopsis phototropin. When brought together by interacting proteins, the fragments reconstitute a functional reporter that permits tagged protein complexes to be visualized by fluorescence light microscopy (LM), and then by standard as well as "multicolor" electron microscopy (EM) via the photooxidation of 3-3'-diaminobenzidine and its derivatives.

Keywords: LOV domain; electron microscopy; protein-protein interactions; split-fluorescent proteins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3,3'-Diaminobenzidine / chemistry
  • Arabidopsis / chemistry
  • Arabidopsis Proteins / chemistry*
  • Cells, Cultured
  • Flavoproteins / chemistry*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Luminescent Proteins / chemistry*
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Oxidation-Reduction
  • Photochemical Processes
  • Protein Binding


  • Arabidopsis Proteins
  • Flavoproteins
  • Luminescent Proteins
  • 3,3'-Diaminobenzidine