Host‐guest scale of left‐handed polyproline II helix formation

Abstract

Despite the clear importance of the left-handed polyproline II (PPII) helical conformation in many physiologically important processes as well as its potential significance in protein unfolded states, little is known about the physical determinants of this conformation. We present here a scale of relative PPII helix-forming propensities measured for all residues, except tyrosine and tryptophan, in a proline-based host peptide system. Proline has the highest measured propensity in this system, a result of strong steric interactions that occur between adjacent prolyl rings. The other measured propensities are consistent with backbone solvation being an important component in PPII helix formation. Side chain to backbone hydrogen bonding may also play a role in stabilizing this conformation. The PPII helix-forming propensity scale will prove useful in future studies of the conformational properties of proline-rich sequences as well as provide insights into the prevalence of PPII helices in protein unfolded states.

Polyproline II propensities from GGXGG peptides reveal an anticorrelation with β-sheet scales

“…It is further encouraging that our data are qualitatively consistent with the scale of Rucker et al (46) derived from a Pro-rich peptide background. The two scales are based on completely different host models and use independent measures (NMR vs. CD).…”

“…Importantly, we find an inverse correlation between the determined PPII scale and the ␤-sheet-forming propensities derived from a zinc-finger model system (45) when 18 aa (except Gly and Pro) are divided into two groups: one, the nonpolar ␤-branched and bulky aromatic residues (VIWFY) and the other all of the remaining side chains. Finally, we find a correlation between our PPII scale in AcGGXGGNH 2 and a PPII scale derived from alternative model peptides such as AcPPPXPPPGYNH 2 (46). Still there are indications that the PPII scale is likely to be sequence and context dependent (47).…”

Helix, Sheet, and Polyproline II Frequencies and Strong Nearest Neighbor Effects in a Restricted Coil Library

“…Finally, the improved coil library is in good qualitative agreement with experimental trends in PPII preferences (39)(40)(41). A recently derived propensity scale for PPII conformations for GGXGG model peptides, obtained using NMR 3 J NH-CRH coupling constants and circular dichroism (Cheng, K.; Kallenbach, N.; et al, unpublished data), correlates well (R ) 0.60) with the PPII preferences in the C R t intern library (Figure 4h).…”

“…However, the two pairs of glycine residues flanking each residue in the experimental model peptides probably do not truly represent the averaged effect of all neighboring residues' side-chains as is the case for the PPII propensities calculated from the C R t intern library. A PPII preference scale derived from a series of longer peptides gives Ala, Gln > Asn > Val (40) and also is consistent with the coil library. Thus, our coil library seemingly captures the essence of PPII preferences in unfolded peptides to the extent that these are known today.…”

Solvation driven conformational transitions in the second transmembrane domain of mycobacteriophage holin

“…16,20 While Pro-rich regions show a preference for the PPII structure, host-guest based analysis using Pro-containing sequences as the host revealed that when Gln, Asp, Gly, and Ala (guest) are incorporated, the guest residues can adopt the PPII form. 21,22 This host-guest analysis using short peptides led to the understanding of how a single amino acid can play an important role in influencing a defined conformation. In a recent finding, the groups of Kallenbach and Rose used a comprehensive analysis to assess how nonproline (Pro -) peptides can adopt PPII-like backbone /-w values.…”