The alphabet of intrinsic disorder

Abstract

The ability of a protein to fold into unique functional state or to stay intrinsically disordered is encoded in its amino acid sequence. Both ordered and intrinsically disordered proteins (IDPs) are natural polypeptides that use the same arsenal of 20 proteinogenic amino acid residues as their major building blocks. The exceptional structural plasticity of IDPs, their capability to exist as heterogeneous structural ensembles and their wide array of important disorder-based biological functions that complements functional repertoire of ordered proteins are all rooted within the peculiar differential usage of these building blocks by ordered proteins and IDPs. In fact, some residues (so-called disorder-promoting residues) are noticeably more common in IDPs than in sequences of ordered proteins, which, in their turn, are enriched in several order-promoting residues. Furthermore, residues can be arranged according to their “disorder promoting potencies,” which are evaluated based on the relative abundances of various amino acids in ordered and disordered proteins. This review continues a series of publications on the roles of different amino acids in defining the phenomenon of protein intrinsic disorder and concerns glutamic acid, which is the second most disorder-promoting residue.

Physicochemical Characterisation of KEIF—The Intrinsically Disordered N-Terminal Region of Magnesium Transporter A

“…KEIF was predicted to belong to the R1 region of the Das-Pappu plot [33,34] in Figure 2b, which predicted that KEIF assumes a globular structure in aqueous solution. Figure 2c shows the disorder propensity per amino acid based on fractional difference (C DisProt − C PDB )/C PDB as described by Uversky (2013) [35]. Overall, the sequence did not seem to contain a substantial amount of disorder-promoting residues, although a cluster of disorder-promoting residues was found closer to the C-terminal end of the sequence (residues Pro-24-Gln-28), suggesting that this part of the peptide has higher propensity for disordered conformations.…”

“…KEIF location is indicated by white circle in Region R1. (c) Disorder propensity per amino acid (C DisProt − C PDB )/C PDB , as described byUversky (2013) [35]. (d) Probability prediction of disordered regions and disordered binding regions using PrDOS (green)[36], IUPred2A (light purple), and ANCHOR2 (dark purple) algorithms[37].…”

A high-throughput screen for transcription activation domains reveals their sequence characteristics and permits reliable prediction by deep learning

“…Prior work showed that this Gcn4 derivative has no inherent AD function and that it can accept a wide variety of natural and synthetic ADs, permitting activation of yeast Gcn4-dependent genes Warfield et al, 2014). By varying the ratio of the four DNA bases separately at codon positions 1, 2, and 3 (Labean and Kauffman, 1993), we made two libraries that either (1) biased the randomized coding sequences for residues normally enriched in IDRs (Uversky, 2014) or (2) that encoded an approximately equal representation of all amino acids.…”

Ensemble characterization of an intrinsically disordered FG‐Nup peptide and its F>A mutant in DMSO‐d6

“…[1][2][3][4] IDPs are represented by a collection of a dynamically inter-converting population of structures, termed an 'ensemble of conformations.' In addition to proteins that are fully disordered, many proteins have significant disordered portions.…”

“…In addition to proteins that are fully disordered, many proteins have significant disordered portions. [1][2][3][4] IDPs are represented by a collection of a dynamically inter-converting population of structures, termed an 'ensemble of conformations.' The free energy required to transition between conformational states within the ensemble does not differ greatly between the various conformations.…”