Structural and dynamics analysis of intrinsically disordered proteins by high-speed atomic force microscopy

Nat Nanotechnol. 2021 Feb;16(2):181-189. doi: 10.1038/s41565-020-00798-9. Epub 2020 Nov 23.

Abstract

Intrinsically disordered proteins (IDPs) are ubiquitous proteins that are disordered entirely or partly and play important roles in diverse biological phenomena. Their structure dynamically samples a multitude of conformational states, thus rendering their structural analysis very difficult. Here we explore the potential of high-speed atomic force microscopy (HS-AFM) for characterizing the structure and dynamics of IDPs. Successive HS-AFM images of an IDP molecule can not only identify constantly folded and constantly disordered regions in the molecule, but can also document disorder-to-order transitions. Moreover, the number of amino acids contained in these disordered regions can be roughly estimated, enabling a semiquantitative, realistic description of the dynamic structure of IDPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Intrinsically Disordered Proteins / genetics
  • Intrinsically Disordered Proteins / metabolism
  • Microscopy, Atomic Force*
  • Molecular Imaging
  • Mutation
  • Protein Conformation
  • Protein Folding
  • Quantitative Structure-Activity Relationship

Substances

  • Intrinsically Disordered Proteins