The alphabet of intrinsic disorder: II. Various roles of glutamic acid in ordered and intrinsically disordered proteins

Uversky, Vladimir N

All the functional and structural peculiarities of IDPs/IDPRs are encoded in their amino acid sequences. It was recognized long ago that there are significant differences between ordered proteins/domains and IDPs/IDPRs at the level of their amino acid sequences. 5, 10, 46 In fact, in comparison with ordered proteins, IDPs/IDPRs are characterized by noticeable biases in their amino acid compositions, 5, 8, 10, [46] [47] [48] containing less of so-called "order-promoting" residues (cysteine, tryptophan, isoleucine, tyrosine, phenylalanine, leucine, histidine, valine, asparagines and methionine, which are mostly hydrophobic residues which are commonly found within the hydrophobic cores of foldable proteins) and more of "disorder-promoting" residues (lysine, glutamine, serine, glutamic acid and proline, which are mostly polar and charged residues, which are typically located at the surface of foldable proteins) (Fig. 1A) .