The denatured state of HIV-1 protease under native conditions
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The denatured state of HIV-1 protease under native conditions. / Rösner, Heike I.; Caldarini, Martina; Potel, Gregory; Malmodin, Daniel; Vanoni, Maria A.; Aliverti, Alessandro; Broglia, Ricardo A.; Kragelund, Birthe B.; Tiana, Guido.
In: Proteins: Structure, Function, and Bioinformatics, Vol. 90, No. 1, 2022, p. 96-109.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The denatured state of HIV-1 protease under native conditions
AU - Rösner, Heike I.
AU - Caldarini, Martina
AU - Potel, Gregory
AU - Malmodin, Daniel
AU - Vanoni, Maria A.
AU - Aliverti, Alessandro
AU - Broglia, Ricardo A.
AU - Kragelund, Birthe B.
AU - Tiana, Guido
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - advanced molecular dynamics
KW - denatured state
KW - NMR
KW - STAPHYLOCOCCAL NUCLEASE
KW - MOLECULAR-DYNAMICS
KW - NMR-SPECTROSCOPY
KW - UNFOLDED STATES
KW - FOLDED MONOMER
KW - SH3 DOMAIN
KW - MODEL-FREE
KW - N-15
KW - PROTEINS
KW - ENSEMBLE
U2 - 10.1002/prot.26189
DO - 10.1002/prot.26189
M3 - Journal article
C2 - 34312913
VL - 90
SP - 96
EP - 109
JO - Proteins: Structure, Function, and Bioinformatics
JF - Proteins: Structure, Function, and Bioinformatics
SN - 0887-3585
IS - 1
ER -
ID: 275830319