Structural proteomics methods to interrogate the conformation and dynamics of intrinsically disordered proteins

Rebecca Beveridge, Antonio N. Calabrese

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)
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Intrinsically disordered proteins (IDPs) and regions of intrinsic disorder (IDRs) are abundant in proteomes and are essential for many biological processes. Thus, they are often implicated in disease mechanisms, including neurodegeneration and cancer. The flexible nature of IDPs and IDRs provides many advantages, including (but not limited to) overcoming steric restrictions in binding, facilitating posttranslational modifications, and achieving high binding specificity with low affinity. IDPs adopt a heterogeneous structural ensemble, in contrast to typical folded proteins, making it challenging to interrogate their structure using conventional tools. Structural mass spectrometry (MS) methods are playing an increasingly important role in characterizing the structure and function of IDPs and IDRs, enabled by advances in the design of instrumentation and the development of new workflows, including in native MS, ion mobility MS, top-down MS, hydrogen-deuterium exchange MS, crosslinking MS, and covalent labeling. Here, we describe the advantages of these methods that make them ideal to study IDPs and highlight recent applications where these tools have underpinned new insights into IDP structure and function that would be difficult to elucidate using other methods.

Original languageEnglish
Article number603639
Number of pages20
JournalFrontiers in Chemistry
Publication statusPublished - 11 Mar 2021


  • mass spectrometry
  • ion mobility
  • Intrinsically disordered protein (IDP)
  • hydrogen deuterium exchange (HDX)
  • crosslinking mass spectrometry (XL-MS)


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