The denatured state of several proteins has been shown to display transient structures that are relevant for folding, stability, and aggregation. To detect them by nuclear magnetic resonance (NMR) spectroscopy, the denatured state must be stabilized by chemical agents or changes in temperature. This makes the environment different from that experienced in biologically relevant processes. Using high-resolution heteronuclear NMR spectroscopy, we have characterized several denatured states of a monomeric variant of HIV-1 protease, which is natively structured in water, induced by different concentrations of urea, guanidinium chloride, and acetic acid. We have extrapolated the chemical shifts and the relaxation parameters to the denaturant-free denatured state at native conditions, showing that they converge to the same values. Subsequently, we characterized the conformational properties of this biologically relevant denatured state under native conditions by advanced molecular dynamics simulations and validated the results by comparison to experimental data. We show that the denatured state of HIV-1 protease under native conditions displays rich patterns of transient native and non-native structures, which could be of relevance to its guidance through a complex folding process.

The denatured state of HIV-1 protease under native conditions / H.I. Rösner, M. Caldarini, G. Potel, D. Malmodin, M.A. Vanoni, A. Aliverti, R.A. Broglia, B.B. Kragelund, G. Tiana. - In: PROTEINS. - ISSN 0887-3585. - 90:1(2022 Jan), pp. 96-109. [10.1002/prot.26189]

The denatured state of HIV-1 protease under native conditions

M. Caldarini;G. Potel;M.A. Vanoni;A. Aliverti;R.A. Broglia;G. Tiana
Ultimo
2022-01

Abstract

The denatured state of several proteins has been shown to display transient structures that are relevant for folding, stability, and aggregation. To detect them by nuclear magnetic resonance (NMR) spectroscopy, the denatured state must be stabilized by chemical agents or changes in temperature. This makes the environment different from that experienced in biologically relevant processes. Using high-resolution heteronuclear NMR spectroscopy, we have characterized several denatured states of a monomeric variant of HIV-1 protease, which is natively structured in water, induced by different concentrations of urea, guanidinium chloride, and acetic acid. We have extrapolated the chemical shifts and the relaxation parameters to the denaturant-free denatured state at native conditions, showing that they converge to the same values. Subsequently, we characterized the conformational properties of this biologically relevant denatured state under native conditions by advanced molecular dynamics simulations and validated the results by comparison to experimental data. We show that the denatured state of HIV-1 protease under native conditions displays rich patterns of transient native and non-native structures, which could be of relevance to its guidance through a complex folding process.
NMR; advanced molecular dynamics; denatured state
Settore BIO/10 - Biochimica
Settore FIS/03 - Fisica della Materia
27-lug-2021
https://onlinelibrary.wiley.com/doi/10.1002/prot.26189
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/860872
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