Sequence-independent recognition of the amyloid structural motif by GFP protein family

Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22122-22127. doi: 10.1073/pnas.2001457117. Epub 2020 Aug 24.

Abstract

Cnidarian fluorescent protein (FP) derivatives such as GFP, mCherry, and mEOS2 have been widely used to monitor gene expression and protein localization through biological imaging because they are considered functionally inert. We demonstrate that FPs specifically bind amyloid fibrils formed from many natural peptides and proteins. FPs do not bind other nonamyloid fibrillar structures such as microtubules or actin filaments and do not bind to amorphous aggregates. FPs can also bind small aggregates formed during the lag phase and early elongation phase of fibril formation and can inhibit amyloid fibril formation in a dose-dependent manner. These findings suggest caution should be taken in interpreting FP-fusion protein localization data when amyloid structures may be present. Given the pathological significance of amyloid-related species in some diseases, detection and inhibition of amyloid fibril formation using FPs can provide insights on developing diagnostic tools.

Keywords: GFP-like proteins; amyloid fibril; binding; inhibition.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amyloidogenic Proteins / chemistry*
  • Green Fluorescent Proteins / chemistry*
  • Humans
  • Luminescent Proteins
  • Microscopy, Confocal / methods*
  • Protein Conformation

Substances

  • Amyloidogenic Proteins
  • Luminescent Proteins
  • red fluorescent protein
  • Green Fluorescent Proteins