Towards Proteomic Approaches for the Identification of Structural Disorder

Veronika      Csizmok; Zsuzsanna      Dosztanyi; Istvan      Simon; Peter      Tompa

Abstract

Intrinsically unstructured/disordered proteins (IUPs) and protein domains lack a well-defined three-dimensional structure under physiological conditions. Structural disorder imparts advantages in many non-conventional functions, which poses a significant challenge to our understanding of the structure-function relationship of proteins. The general appreciation of this fact, however, is hampered by the large gap in our knowledge on IUPs, as we have biophysical data on less than 500 of them, whereas bioinformatic predictions suggest at least several thousand such proteins in the human proteome alone. Thus, proteomic-scale identification and characterization of IUPs will need to be implemented to fill this gap and advance our knowledge in this important field. In this review we give an insight into the various rationales of proteomic efforts of identifying IUPs, and survey the handful of attempts that combined enrichment of extracts for IUPs by heat- or acid treatment with a subsequent two-dimensional electrophoresis/mass spectrometry identification. Advantages and drawbacks of the various approaches are outlined in anticipation of future inventions in the field that will hopefully elevate IUP research to the truly proteomic level.

Keywords: Intrinsically unstructured protein, intrinsically disordered protein, natively unfolded protein, structural genomics, structural proteomics, target prioritization, target filtering, structure solution pipeline