Structural characterization of intrinsically disordered proteins by NMR spectroscopy

Molecules. 2013 Sep 4;18(9):10802-28. doi: 10.3390/molecules180910802.

Abstract

Recent advances in NMR methodology and techniques allow the structural investigation of biomolecules of increasing size with atomic resolution. NMR spectroscopy is especially well-suited for the study of intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) which are in general highly flexible and do not have a well-defined secondary or tertiary structure under functional conditions. In the last decade, the important role of IDPs in many essential cellular processes has become more evident as the lack of a stable tertiary structure of many protagonists in signal transduction, transcription regulation and cell-cycle regulation has been discovered. The growing demand for structural data of IDPs required the development and adaption of methods such as 13C-direct detected experiments, paramagnetic relaxation enhancements (PREs) or residual dipolar couplings (RDCs) for the study of 'unstructured' molecules in vitro and in-cell. The information obtained by NMR can be processed with novel computational tools to generate conformational ensembles that visualize the conformations IDPs sample under functional conditions. Here, we address NMR experiments and strategies that enable the generation of detailed structural models of IDPs.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Intrinsically Disordered Proteins / metabolism
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Protein Processing, Post-Translational

Substances

  • Intrinsically Disordered Proteins