Single-molecule fluorescence studies of intrinsically disordered proteins and liquid phase separation

Biochim Biophys Acta Proteins Proteom. 2019 Oct;1867(10):980-987. doi: 10.1016/j.bbapap.2019.04.007. Epub 2019 May 2.

Abstract

Intrinsically disordered proteins (IDPs) are ubiquitous in proteomes and serve in a range of cellular functions including signaling, regulation, transport and enzyme function. IDP misfunction and aggregation are also associated with several diseases including neurodegenerative diseases and cancer. During the past decade, single-molecule methods have become popular for detailed biophysical and structural studies of these complex proteins. This work has included recent applications to cellular liquid-liquid phase separation (LLPS), relevant for functional dynamics of membraneless organelles such as the nucleolus and stress granules. In this concise review, we cover the conceptual motivations for development and application of single-molecule fluorescence methods for such IDP studies. We follow with a few key examples of systems and biophysical problems that have been addressed, and conclude with thoughts for emerging and future directions.

Keywords: Intrinsically disordered proteins; Liquid-liquid phase separation; Single-molecule FRET; Single-molecule biophysics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Nucleolus* / chemistry
  • Cell Nucleolus* / metabolism
  • Cytoplasmic Granules* / chemistry
  • Cytoplasmic Granules* / metabolism
  • Humans
  • Intrinsically Disordered Proteins* / chemistry
  • Intrinsically Disordered Proteins* / metabolism
  • Molecular Imaging
  • Neurodegenerative Diseases / metabolism*
  • Protein Aggregates*

Substances

  • Intrinsically Disordered Proteins
  • Protein Aggregates