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• W2058657681 startingPage "15318" @default.
• W2058657681 abstract "Molten globules are compact, partially folded proteins postulated to be general intermediates in protein folding. Human α-lactalbumin (α-LA) is a two-domain Ca2+-binding protein that partially unfolds at low pH to form a molten globule. NMR spectra of molten globules are characterized by broadened resonances due to conformational fluctuations on microsecond to millisecond time scales. These species are often studied at high temperature where NMR resonances are observed to sharpen. The effect of higher temperatures on fast time-scale backbone dynamics of molten globules has not been investigated previously. Here, 1D 15N direct-detection and 2D indirect-detection 1H−15N heteronuclear NOE experiments have been used to probe fast time-scale dynamics at low and high temperatures for three disulfide-bond variants of human α-LA that form molten globules. Disulfide bonds are found to have a significant effect on backbone dynamics within the β-domain of the molten globule; within the α-domain, dynamics are not significantly influenced by these bonds. At 20 °C, backbone mobility is significantly decreased in both domains of the molten globule compared to the mobility at 40−50 °C. Heteronuclear NOE values determined at 20 °C for the α-domain are closely similar to those observed for native α-LA, indicating that the α-LA molten globule has even more native-like character than suggested by studies conducted at higher temperature. Our results highlight the importance of considering the temperature dependence of the molten globule ensemble when making comparisons between experimental data obtained under different conditions." @default.
• W2058657681 created "2016-06-24" @default.
• W2058657681 creator A5029960984 @default.
• W2058657681 creator A5047204586 @default.
• W2058657681 date "2008-10-22" @default.
• W2058657681 modified "2023-10-03" @default.
• W2058657681 title "Probing the Effect of Temperature on the Backbone Dynamics of the Human α-Lactalbumin Molten Globule" @default.
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• W2058657681 doi "https://doi.org/10.1021/ja802967k" @default.
• W2058657681 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18939797" @default.
• W2058657681 hasPublicationYear "2008" @default.
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