Comparison of folding rate constants (KF), activation energy of folding (ΔG[Ea]F), and the entropy barrier (TΔS[F]) for spontaneous and GroEL-ES-assisted refolding of DapA and spontaneous refolding of MsNanA

Range Table - link
Organism Unspecified
Reference Georgescauld F et al., GroEL/ES chaperonin modulates the mechanism and accelerates the rate of TIM-barrel domain folding. Cell. 2014 May 8 157(4):922-34. doi: 10.1016/j.cell.2014.03.038. Supplemental Information table S2PubMed ID24813614
Method Abstract: "Here, [investigators] analyzed the folding of DapA at peptide resolution using hydrogen/deuterium exchange and mass spectrometry."
Comments P.926 left column bottom paragraph: "The population of highly dynamic folding intermediates by DapA suggested the presence of a significant entropic component of the kinetic barrier to folding. Consistent with this notion, the spontaneous folding rate of DapA proved temperature independent between 15°C and 25°C (Figure S3F Table S2) (Bicout and Szabo, 2000, Dobson et al., 1998 and Matagne et al., 2000). Below 15°C, the Arrhenius plot displayed a constant slope, reflecting a transition state with both enthalpic and entropic components (Dobson et al., 1998) (Table S2). The Arrhenius plot of GroEL/ES-assisted folding displayed a linear slope over the entire temperature range from 7.5°C to 25°C (Figure S3F), indicating that the activation barrier has gained a significant enthalpic component and the entropic contribution is reduced (Table S2). To extend this analysis to 37°C, [investigators] performed refolding experiments with single-molecule detection (100 pM DapA see Figure 2C). Identical rates of spontaneous refolding of DapA-293C-Alexa were measured at 20°C and 37°C (Figures 2C and S3G), suggesting that the non-Arrhenius behavior extends to 37°C. In contrast, the rate of assisted folding increased ∼2-fold from 20°C to 37°C, resulting in an ∼130-fold acceleration of folding by GroEL/ES over the spontaneous rate at the physiological temperature (Figures 2C and S3G). The spontaneous renaturation of MsNanA displayed a similar temperature dependence as the assisted refolding of DapA (Figure S3F Table S2), suggesting that GroEL/ES shifts the folding properties of DapA toward those of the chaperonin-independent MsNanA." See text beneath table
Entered by Uri M
ID 112599