Application of native mass spectrometry in studying intrinsically disordered proteins: A special focus on neurodegenerative diseases

Abstract

Intrinsically disordered proteins (IDPs) are integral part of the proteome, regulating vital biological processes. Such proteins gained further visibility due to their key role in neurodegenerative diseases and cancer. IDPs however, escape structural characterization by traditional biophysical tools owing to their extreme flexibility and heterogeneity. In this review, we discuss the advantages of native mass spectrometry (MS) in analysing the atypical conformational dynamics of IDPs and recent advances made in the field. Especially, MS studies unravelling the conformational facets of IDPs involved in neurodegenerative diseases are highlighted. The limitations and the future promises of native MS while studying IDPs have been discussed.

Keywords: Conformational disorder; Intrinsically disordered protein; Ion mobility mass spectrometry; Native mass spectrometry; Neurodegenerative disease; Protein oligomer.