Phl p 7 exhibits atypical conformational stability and a diminutive denaturational heat capacity increment, ΔCp. Because exposure of apolar surface largely dictates the magnitude of ΔCp, a depressed value could signify an unusually compact unfolded state. The volume of the denatured state ensemble (DSE) is evidently inversely correlated with mean hydrophobicity [Pace et al., Protein Sci. 19 (2010) 929–943]. Interestingly, apolar residues replace more polar ones at four positions in Phl p 7. We herein examine the consequences of replacing those residues with the corresponding ones from Bra n 1, a related isoform. All four mutations – M4H, L21A, I60T, and C63A – destabilize Phl p 7. ... More
Phl p 7 exhibits atypical conformational stability and a diminutive denaturational heat capacity increment, ΔCp. Because exposure of apolar surface largely dictates the magnitude of ΔCp, a depressed value could signify an unusually compact unfolded state. The volume of the denatured state ensemble (DSE) is evidently inversely correlated with mean hydrophobicity [Pace et al., Protein Sci. 19 (2010) 929–943]. Interestingly, apolar residues replace more polar ones at four positions in Phl p 7. We herein examine the consequences of replacing those residues with the corresponding ones from Bra n 1, a related isoform. All four mutations – M4H, L21A, I60T, and C63A – destabilize Phl p 7. Our analysis suggests that the DSE of Phl p 7 is indeed highly compact and that the substitutions act by increasing its volume and solvent-accessibility. All four mutations increase the urea m value; L21A, I60T, and C63A also yield a perceptible increase in ΔCp.
