Helicity of short E‐R/K peptides

Abstract

Understanding the secondary structure of peptides is important in protein folding, enzyme function, and peptide-based drug design. Previous studies of synthetic Ala-based peptides (>12 a.a.) have demonstrated the role for charged side chain interactions involving Glu/Lys or Glu/Arg spaced three (i, i 1 3) or four (i, i 1 4) residues apart. The secondary structure of short peptides (<9 a.a.), however, has not been investigated. In this study, the effect of repetitive Glu/Lys or Glu/Arg side chain interactions, giving rise to E-R/K helices, on the helicity of short peptides was examined using circular dichroism. Short E-R/K-based peptides show significant helix content. Peptides containing one or more E-R interactions display greater helicity than those with similar E-K interactions. Significant helicity is achieved in Arg-based E-R/K peptides eight, six, and five amino acids long. In these short peptides, each additional i 1 3 and i 1 4 salt bridge has substantial contribution to fractional helix content. The E-R/K peptides exhibit a strongly linear melt curve indicative of noncooperative folding. The significant helicity of these short peptides with predictable dependence on number, position, and type of side chain interactions makes them an important consideration in peptide design.

The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage

“…For temperature melts elipticity at 222 nm was monitored over a temperature range of 10°C to 70°C with a temperature slope of 1°C/min and protein concentrations were in the 25–35 $\mu$M range. Raw data sets were corrected for buffer contributions and converted to percent helicity as previously described (Sommese et al, 2010; Chen et al, 1974). …”

Characterization of long and stable de novo single alpha-helix domains provides novel insight into their stability

“…However, the equivalent study for E–R pairs is lacking. Although it was recently reported that E–R pairs may be more stabilizing than E–K in very short (<12 residue) peptides20, it is unclear which pairings are utilized, or why E–R pairs are more stabilizing.…”

Determinants of Helix Formation for a Kv1.3 Transmembrane Segment inside the Ribosome Exit Tunnel

“…4A bottom), which is ideally situated to form a salt-bridge with native E247 ( i , i +4) 45–47 . We chose an R in preference to lysine (K) because properly spaced E-R residues form a helix inside the tunnel 48 and, in solution, have higher helix content than their E-K counterparts 4 . The 243R mutation yields a nascent chain that is compact (Fig.…”

“…The first step appears to be acquisition of local secondary structures, e.g., helices and turns, followed by folding to a more global native structure 2, 3 . Helix formation depends on the protein’s primary sequence, its solvent environment, and the combination of physicochemical properties that underlie intrahelical side-chain interactions, helical dipole (charge-dipole) interactions, and the effects of other residues flanking the helix 4, 5 . Despite the importance and ubiquity of helical structures in mature proteins, the question of when/where/how these critical structures arise during early biogenesis is still largely unanswered.…”