Roles, Characteristics, and Analysis of Intrinsically Disordered Proteins: A Minireview

Abstract

In recent years, there has been a growing understanding that a significant fraction of the eukaryotic proteome is intrinsically disordered, and that these conformationally dynamic proteins play a myriad of vital biological roles in both normal and pathological states. In this review, selected examples of intrinsically disordered proteins are highlighted, with particular attention for a few which are relevant in neurological disorders and in viral infection. Next, the underlying causes for the intrinsic disorder are discussed, along with computational methods used to predict whether a given amino acid sequence is likely to adopt a folded or unfolded state in the solution. Finally, biophysical methods for the analysis of intrinsically disordered proteins will be discussed, as well as the unique challenges they pose in this context due to their highly dynamic nature.

Impact of charge state on 193 nm ultraviolet photodissociation of protein complexes

“…Although ETD and ECD have been applied successfully for dissociation of supercharged complexes in high charge states, fragmentation was limited for lower charge states generated from standard native or charge-reducing solutions. 21,23,24,32,33 The limited fragmentation was attributed to the significant dependence of the energy deposition of electron activation on precursor charge that has been consistently reported for electron-based activation methods.…”

“…[10][11][12] With only ~14% of proteins functioning as monomers, understanding the networks of noncovalent interactions that create the protein architectures and stabilize protein assemblies is crucial to providing insight into molecular processes. 13 To that end, ESI-MS along with various activation methods have been employed to probe the stability, 5,[14][15][16][17][18] assembly and unfolding, 15,17,[19][20][21] topology, [15][16][17]22 and primary sequence 18,[21][22][23][24] of multimeric proteins.…”

“…5 Electron-based activation methods, such as electron transfer and electron capture dissociation (ETD and ECD, respectively), result in production of sequence ions that arise from backbone cleavages in the most surface exposed regions of proteins. 21,23,24,32,33 Noncovalent interactions can be preserved during ETD and ECD, generating sequence ions that still retain a ligand, referred to as holo-fragments. Such holo-fragments are useful in localizing the active sites of proteins.…”

“…Such holo-fragments are useful in localizing the active sites of proteins. 21,23,24,32,33 Both the efficiency of electron-based dissociation and the production of holo-fragments increased with precursor charge state. 21,23,24,32,33 In an outcome similar to that observed for collisional activation, asymmetric charge partitioning of ejected monomers was observed upon electron activation of protein complexes, and a means to quantify this phenomenon based on an asymmetric charge partitioning factor (ACPF, Eq.…”

Function, Regulation, and Dysfunction of Intrinsically Disordered Proteins

“…In this issue of Life , a collection of articles is presented with the specific focus of describing the “Functions, Regulation and Dysfunction of Intrinsically Disordered Proteins”. Lermyte et al [ 1 ] provided a comprehensive review on IDPs, devoting a particular attention to some disordered systems of relevance for neurological disorders as well as viral infections. The biological properties of IDPs are described vis-à-vis an analysis of the biophysical methods that have been recently optimised to study the structural properties of IDPs.…”