Conformational transitions provoked by organic solvents in β-lactoglobulin: can a molten globule like intermediate be induced by the decrease in dielectric constant?

Uversky, Vladimir N.; Narizhneva, Natalya V.; Kirschstein, S.; Winter, Stefan; Löber, G.

doi:10.1016/s1359-0278(97)00023-0

Cited by 183 publications

(152 citation statements)

References 39 publications

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“…The environmental effect of the ␣-helix template may resemble the solvent effect of alcohols. Alcohols enhance the ␣-helix (25,(38)(39)(40)(41) and destabilize the PPII helix, which is correlated with the solvent polarity of alcohols (28). These results suggest that alcohols strengthen the electrostatic interactions, primarily hydrogen bonds, resulting in an increase in the ␣-helix (42) and a decrease in the PPII helix.…”

Section: Resultsmentioning

confidence: 90%

Secondary structure provides a template for the folding of nearby polypeptides

Kameda

Takada

2006

Proc. Natl. Acad. Sci. U.S.A.

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Although protein structures are primarily encoded by their sequences, they are also critically dependent on environmental factors such as solvents and interactions with other molecules. Here we investigate how the folding-energy landscape of a short peptide is altered by interactions with another peptide, by performing atomistic replica-exchange molecular dynamics simulations of polyalanines in various environments. We analyzed the free-energy landscapes of Ala 7 and Ala 8 in isolation, near an ␣-helix template, and near a ␤-strand template. The isolated Ala 7 and Ala 8 at 270 K were mainly in polyproline II helix conformations and in equilibrium between the ␣-helix and polyproline II helix, respectively, in harmony with the experiment. Interestingly, we found remarkably strong secondary-structure ''templating''; namely, the ␣-helix template enhanced ␣-helix conformation and the ␤-strand template induced ␤-strand conformation in the simulated Ala 8 . The ␣-helix template lowered the nearby dielectric constant, which strengthened hydrogen bonds in the simulated Ala 8 , leading to ␣-helix stabilization. The ␤-strand template provided hydrogen bond positions to the simulated Ala 8 , sharply inducing ␤-strand structure. With or without templates, the energy landscape of Ala 8 is always funnel-like and centered at the ␣-helix conformation, whereas entropic contribution disfavors the ␣-helix, leading to subtle competition. Secondary-structure templating may play a critical role in protein conformation dynamics in the cellular environment.energy landscape ͉ generalized Born ͉ polyproline II ͉ protein folding ͉ replica exchange P rotein structures are primarily encoded by their sequences, and many proteins can spontaneously fold into their native structures. This robust refolding can be realized through organization of the funnel-like energy landscape (1). However, many cases where the protein environment makes the situation substantially more complex need further consideration, such as domain swapping in multidomain proteins (2), amyloid formation (3), and nonspecific macromolecular crowding (4). In general, environmental factors such as protein-protein and protein-solvent interactions change the energy landscape of proteins, leading to critical differences in conformational states, which could be an important source of biological diversity.Environmental effects on protein conformation are very versatile, even for one of the simplest polypeptides, polyalanine, and its derivatives. Ala 13 , flanked by two ornithine-and alaninerich peptides containing interior lysine, glutamic acid, or glutamine, favors an ␣-helix structure in water (5-7), which is consistent with the high propensity of alanine to take on an ␣-helix structure in the statistics of the Protein Data Bank (8). However, similar alanine-based peptides, Ala-Gly-Ala-Ala-AlaAla-Gly-Ala (9) and Ac-Lys-Ala 14 -Lys-methyl amide (NMe) (10), form amyloid fibrils in water. In a more complicated way, shorter alanines (Ala n with n Ϸ 10) flanked by Lys are in disordered ...

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Section: Resultsmentioning

confidence: 90%

Secondary structure provides a template for the folding of nearby polypeptides

Kameda

Takada

2006

Proc. Natl. Acad. Sci. U.S.A.

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“…34 A similar correlation between helix formation and dielectric constant has been seen in experiments on b-lactoglobulin in organic solvents. 35 Therefore, the formation of tertiary structure, which introduces more low-dielectric material into the environment of the backbone amides, strengthens the H-bonds responsible for stabilizing secondary structure. This explains the cooperativity observed in most of Figure 4 (e.g.…”

Section: The Acid-unfolded Stagementioning

confidence: 99%

Structural Details, Pathways, and Energetics of Unfolding Apomyoglobin

Onufriev

Case

Bashford

2003

Journal of Molecular Biology

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Protein folding is often difficult to characterize experimentally because of the transience of intermediate states, and the complexity of the proteinsolvent system. Atomistic simulations, which could provide more detailed information, have had to employ highly simplified models or high temperatures, to cope with the long time scales of unfolding; direct simulation of folding is even more problematic. We report a fully atomistic simulation of the acid-induced unfolding of apomyoglobin in which the protonation of acidic side-chains to simulate low pH is sufficient to induce unfolding at room temperature with no added biasing forces or other unusual conditions; and the trajectory is validated by comparison to experimental characterization of intermediate states. Novel insights provided by their analysis include: characterization of a dry swollen globule state forming a barrier to initial unfolding or final folding; observation of cooperativity in secondary and tertiary structure formation and its explanation in terms of dielectric environments; and structural details of the intermediate and the completely unfolded states. These insights involve time scales and levels of structural detail that are presently beyond the range of experiment, but come within reach through the simulation methods described here. An implicit solvation model is used to analyze the energetics of protein folding at various pH and ionic strength values, and a reasonable estimate of folding free energy is obtained. Electrostatic interactions are found to disfavor folding.

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“…24 Three-, four-and five-state unfolding processes of some proteins by different denaturants have been reported by some researchers. [25][26][27][28][29] These works not only need fluorescence spectroscopy, nuclear magnetic resonance spectroscopy, circular dichroism spectroscopy, infrared spectroscopy, size exclusion chromatography and other physical and chemical means, but require complex testing and complicated calculations. However, to our knowledge, there have been no reports on the stable conformational state distribution during the protein unfolding process by electrochemical method.…”

Section: Introductionmentioning

confidence: 99%

Investigation on the Conformation Change of Hemoglobin Immobilized on MPA-modified Electrode by Electrochemical Method

Yan

Zheng

et al. 2013

ANAL. SCI.

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The conformation change of bovine hemoglobin (Hb) during the unfolding process induced by urea and acid was investigated by an electrochemical method. Hb unfolding induced by urea of different concentrations was realized by bonding Hb onto a 3-mercaptopropionic acid (MPA) modified gold electrode. The difference in unfolding percentage showed that the Hb unfolding induced by urea was a two-step, three-state transition process, while the unfolding induced by acid was a two-state transition process. The results obtained by the electrochemical method coincided closely with those obtained by UV-vis spectroscopy and fluorescence spectroscopy. Some thermodynamic parameters during the conformational change were also calculated to study the intermediate state during the Hb unfolding process. The present work may lead to an easy and effective way to study metalloproteins unfolding, and holds great promise for the design of novel sensitive biosensors.

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Conformational transitions provoked by organic solvents in β-lactoglobulin: can a molten globule like intermediate be induced by the decrease in dielectric constant?

Cited by 183 publications

References 39 publications

Secondary structure provides a template for the folding of nearby polypeptides

Secondary structure provides a template for the folding of nearby polypeptides

Structural Details, Pathways, and Energetics of Unfolding Apomyoglobin

Investigation on the Conformation Change of Hemoglobin Immobilized on MPA-modified Electrode by Electrochemical Method

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