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

Uversky, Vladimir N

Glutamic acid in the Ramachandran plot. The structure of a protein can be described using torsion angles-φ and ψ-of its backbone that provides a simple view of the conformation of a protein. In sequence order, φ is the N i-1 -C i -Cα i -N i torsion angle, and ψ is the C i -Cα i -N i -C i+1 torsion angle. Since most combinations of φ and ψ are sterically forbidden, the 2D plot of the torsion angles of the protein backbone, known as the Ramachandran plot, 61 provides a simple view of the conformation of a protein, since the φ-ψ angles cluster into distinct regions in the Ramachandran plot, where each region corresponds to a particular secondary structure. In the generic Ramachandran plot (see Fig. 2B ) that refers to the 18 non-glycine and non-proline amino acids, there are four distinct regions of density (the α (right-handed α-helix region), α L (mirror image of α), β S (region largely involved in β-sheet formation) and β P (region associated with extended polyproline-like helices but also observed in β-sheet). The shape of the generic Ramachandran plot is determined mainly by the presence of specific steric clashes 61 and backbone dipole-dipole interactions. [62] [63] [64] Glutamic acid in electrostatic interactions and hydrogen bonds. Glutamic acid participates in electrostatic interactions, which are also known as ionic bonds, or salt bridges, or salt GCN4 leucine zipper dimer revealed that the free energy of helix stabilization associated with the hydrogen-bonding and hydrophobic interactions in this capping structure is −1.2 kcal/ mol, illustrating that helix capping might play a significant role in protein folding. 72 Based on the analysis of 431 α-helices the normalized frequencies for finding particular residues at the C cap position, the average fraction of buried surface area and the hydrogen bonding patterns of the C cap residue side-chain were calculated. 74 This analysis revealed that the residue found in the C cap position is on average 70% buried and that there is a noticeable correlation between the relative burial of this residue and its hydrophobicity. 74 Furthermore, C cap residues with polar sidechains were shown to be involved in hydrogen bonding, where the longer side-chains of glutamic acid, glutamin, arginine, lysine and histidine form hydrogen bonds with residues located more than four residues apart, whereas the shorter side-chains Glutamic acid and protein secondary structure. Although protein secondary structure is determined by hydrogen bonds between donor and acceptor groups in the protein backbone, different amino acids are known to favor the formation of different secondary structure elements, such as α-helices, β-pleated sheets or loops. The α-helix-formers include alanine, cysteine, leucine, methionine, glutamic acid, glutamine, histidine and lysine, whereas valine, isoleucine, phenylalanine, tyrosine, tryptophan and threonine favor β-structure formation, and serine, glycine, uncharged aspartic acid, asparagine and proline are found most often in β-turns. It was pointed out that there is no apparent relationship between the chemical nature of the amino acid side chain and its secondary structure preferences. For example, although glutamic and aspartic acids are closely related chemically, glutamic acid is more likely to be found in helices and aspartic acid is predominantly located in β-turns. In fact, the helical propensity of glutamic acid is 0.40, whereas aspartic acid has an helical propensity of 0.