Molecular mechanisms of pressure induced conformational changes in BPTI

Wroblowski, Berthold; Díaz, J. Fernando; Heremans, Karel; Engelborghs, Yves

doi:10.1002/(sici)1097-0134(199608)25:4<446::aid-prot5>3.0.co;2-b

Cited by 19 publications

(7 citation statements)

References 37 publications

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“…A recent study 42 supports this interpretation of the denaturing effects of pressure: by using molecular dynamics calculations it was shown that pressure encourages water penetration into the hydrophobic core of BPTI, which was used as a model molecule. So, it is likely that the F31A mutant is much more accessible to the solvent than the wild type and consequently more prone to pressure-induced denaturation.…”

Section: Discussionmentioning

confidence: 79%

Extreme heat‐ and pressure‐resistant 7‐kDa protein P2 from the archaeon Sulfolobus solfataricus is dramatically destabilized by a single‐point amino acid substitution

Fusi¹,

Goossens²,

Consonni³

et al. 1997

Proteins

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This study reports the characterization of the recombinant 7-kDa protein P2 from Sulfolobus solfataricus and the mutants F31A and F31Y with respect to temperature and pressure stability. As observed in the NMR, FTIR, and CD spectra, wild-type protein and mutants showed substantially similar structures under ambient conditions. However, midpoint transition temperatures of the denaturation process were 361, 334, and 347 K for wild type, F31A, and F31Y mutants, respectively: thus, alanine substitution of phenylalanine destabilized the protein by as much as 27 K. Midpoint transition pressures for wild type and F31Y mutant could not be accurately determined because they lay either beyond (wild type) or close to (F31Y) 14 kbar, a pressure at which water undergoes a phase transition. However, a midpoint transition pressure of 4 kbar could be determined for the F31A mutant, implying a shift in transition of at least 10 kbar. The pressure-induced denaturation was fully reversible; in contrast, thermal denaturation of wild type and mutants was only partially reversible. To our knowledge, both the pressure resistance of protein P2 and the dramatic pressure and temperature destabilization of the F31A mutant are unprecedented. These properties may be largely accounted for by the role of an aromatic cluster where Phe31 is found at the core, because interactions among aromatics are believed to be almost pressure insensitive; furthermore, the alanine substitution of phenylalanine should create a cavity with increased compressibility and flexibility, which also involves an impaired pressure and temperature resistance.

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Section: Discussionmentioning

confidence: 79%

Extreme heat‐ and pressure‐resistant 7‐kDa protein P2 from the archaeon Sulfolobus solfataricus is dramatically destabilized by a single‐point amino acid substitution

Fusi¹,

Goossens²,

Consonni³

et al. 1997

Proteins

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“…3,4 Thus, these macromolecules are able to switch their conformations upon sensing environmental perturbations. There are a variety of such perturbations, such as interaction with another macromolecule, 1,5 interaction with a ligand, 6 solvent conditions 7–10 -(polarity and pH), physical environment 11–15 (salt, pressure, temperature, and light), or post-translational modifications. 13,16 …”

mentioning

confidence: 99%

Mapping Allostery through Computational Glycine Scanning and Correlation Analysis of Residue–Residue Contacts

et al. 2015

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Understanding allosteric mechanisms is essential for the physical control of molecular switches and downstream cellular responses. However, it is difficult to decode essential allosteric motions in a high-throughput scheme. A general two-pronged approach to performing automatic data reduction of simulation trajectories is presented here. The first step involves coarse-graining and identifying the most dynamic residue–residue contacts. The second step is performing principal component analysis of these contacts and extracting the large-scale collective motions expressed via these residue–residue contacts. We demonstrated the method using a protein complex of nuclear receptors. Using atomistic modeling and simulation, we examined the protein complex and a set of 18 glycine point mutations of residues that constitute the binding pocket of the ligand effector. The important motions that are responsible for the allostery are reported. In contrast to conventional induced-fit and lock-and-key binding mechanisms, a novel “frustrated-fit” binding mechanism of RXR for allosteric control was revealed.

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“…[19] Kitchen et al [20] first modeled bovine pancreatic trypsin inhibitor (BPTI, 58 residues) under high pressure (10 kbar) but they found no change in the changes in the conformation. Thereafter, Wroblowski et al [21] increased the pressure (20 kbar) and time (800 ps) for the same simulation and found modifications in the secondary structure of BPTI. Hünenberger et al [22] performed simulations on the lysozyme (148 residues) under 10 kbar for 210 ps and obtained no net unfolding.…”

Section: Introductionmentioning

confidence: 88%

Insights of Pressure‐induced Unfolding of β‐Lactoglobulin as Revealed by Steered Molecular Dynamics

Zhang

et al. 2019

Advcd Theory and Sims

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High hydrostatic pressure (HHP) has been widely used in various industries, and the protein as one of the most noticeable bio-macromolecules has exhibited distinct structural and functional characteristics under HHP conditions. In this work, steered molecular dynamics (SMD) simulations of β-lactoglobulin (βlg) are exploited to investigate the flexibility of the individual secondary structural element of the polypeptide. The two loops and the two helices on the two sides of the molecular β-barrel are found to be highly flexible and migrate toward the hydrophobic interior of the protein at relatively low pressures. Interestingly, there is evidence illustrating that water penetrations only occur from the loop-side of the barrel under pressurizations, which is favored by the enlarged β-barrel induced through the loop compression. Moreover, increased stability of βlg is attributed to the rigid regions of the protein molecule. N-and C-termini of the polypeptide chain are also found to be of great importance to pressure-induced unfolding of βlg. It is found the modeling results agree with previous experimental observations, demonstrating the validity of the applications of SMD for studies on pressure-induced protein unfolding. Such methodology will provide new insight into HHP and be generalized for more complicated systems such as enzymes.

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Molecular mechanisms of pressure induced conformational changes in BPTI

Cited by 19 publications

References 37 publications

Extreme heat‐ and pressure‐resistant 7‐kDa protein P2 from the archaeon Sulfolobus solfataricus is dramatically destabilized by a single‐point amino acid substitution

Extreme heat‐ and pressure‐resistant 7‐kDa protein P2 from the archaeon Sulfolobus solfataricus is dramatically destabilized by a single‐point amino acid substitution

Mapping Allostery through Computational Glycine Scanning and Correlation Analysis of Residue–Residue Contacts

Insights of Pressure‐induced Unfolding of β‐Lactoglobulin as Revealed by Steered Molecular Dynamics

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