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An experimental point of view on hydration/solvation in halophilic proteins.

ABSTRACT: Protein-solvent interactions govern the behaviors of proteins isolated from extreme halophiles. In this work, we compared the solvent envelopes of two orthologous tetrameric malate dehydrogenases (MalDHs) from halophilic and non-halophilic bacteria. The crystal structure of the MalDH from the non-halophilic bacterium Chloroflexus aurantiacus (Ca MalDH) solved, de novo, at 1.7 Å resolution exhibits numerous water molecules in its solvation shell. We observed that a large number of these water molecules are arranged in pentagonal polygons in the first hydration shell of Ca MalDH. Some of them are clustered in large networks, which cover non-polar amino acid surface. The crystal structure of MalDH from the extreme halophilic bacterium Salinibacter ruber (Sr) solved at 1.55 Å resolution shows that its surface is strongly enriched in acidic amino acids. The structural comparison of these two models is the first direct observation of the relative impact of acidic surface enrichment on the water structure organization between a halophilic protein and its non-adapted counterpart. The data show that surface acidic amino acids disrupt pentagonal water networks in the hydration shell. These crystallographic observations are discussed with respect to halophilic protein behaviors in solution.

SUBMITTER: Talon R

PROVIDER: S-EPMC3930881 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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An experimental point of view on hydration/solvation in halophilic proteins.

Talon Romain R Coquelle Nicolas N Madern Dominique D Girard Eric E

Frontiers in microbiology 20140221

Protein-solvent interactions govern the behaviors of proteins isolated from extreme halophiles. In this work, we compared the solvent envelopes of two orthologous tetrameric malate dehydrogenases (MalDHs) from halophilic and non-halophilic bacteria. The crystal structure of the MalDH from the non-halophilic bacterium Chloroflexus aurantiacus (Ca MalDH) solved, de novo, at 1.7 Å resolution exhibits numerous water molecules in its solvation shell. We observed that a large number of these water mol ...[more]

PMID: 24600446

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Project description:BACKGROUND: Accurate description of protein interaction with aqueous solvent is crucial for modeling of protein folding, protein-protein interaction, and drug design. Efforts to build a working description of solvation, both by continuous models and by molecular dynamics, yield controversial results. Specifically constructed knowledge-based potentials appear to be promising for accounting for the solvation at the molecular level, yet have not been used for this purpose. RESULTS: We developed original knowledge-based potentials to study protein hydration at the level of atom contacts. The potentials were obtained using a new Monte Carlo reference state (MCRS), which simulates the expected probability density of atom-atom contacts via exhaustive sampling of structure space with random probes. Using the MCRS allowed us to calculate the expected atom contact densities with high resolution over a broad distance range including very short distances. Knowledge-based potentials for hydration of protein atoms of different types were obtained based on frequencies of their contacts at different distances with protein-bound water molecules, in a non-redundant training data base of 1776 proteins with known 3D structures. Protein hydration sites were predicted in a test set of 12 proteins with experimentally determined water locations. The MCRS greatly improves prediction of water locations over existing methods. In addition, the contribution of the energy of macromolecular solvation into total folding free energy was estimated, and tested in fold recognition experiments. The correct folds were preferred over all the misfolded decoys for the majority of proteins from the improved Rosetta decoy set based on the structure hydration energy alone. CONCLUSION: MCRS atomic hydration potentials provide a detailed distance-dependent description of hydropathies of individual protein atoms. This allows placement of water molecules on the surface of proteins and in protein interfaces with much higher precision. The potentials provide a means to estimate the total solvation energy for a protein structure, in many cases achieving a successful fold recognition. Possible applications of atomic hydration potentials to structure verification, protein folding and stability, and protein-protein interactions are discussed.

Project description:Halophilic proteins have greater abundance of acidic over basic and very low bulky hydrophobic residues. Classical electrostatic stabilization was suggested as the key determinant for halophilic adaptation of protein. However, contribution of specific electrostatic interactions (i.e. salt-bridges) to overall stability of halophilic proteins is yet to be understood. To understand this, we use Adaptive-Poison-Boltzmann-Solver Methods along with our home-built automation to workout net as well as associated component energy terms such as desolvation energy, bridge energy and background energy for 275 salt-bridges from 20 extremely halophilic proteins. We then perform extensive statistical analysis on general and energetic attributes on these salt-bridges. On average, 8 salt-bridges per 150 residues protein were observed which is almost twice than earlier report. Overall contributions of salt-bridges are -3.0 kcal mol-1. Majority (78%) of salt-bridges in our dataset are stable and conserved in nature. Although, average contributions of component energy terms are equal, their individual details vary greatly from one another indicating their sensitivity to local micro-environment. Notably, 35% of salt-bridges in our database are buried and stable. Greater desolvation penalty of these buried salt-bridges are counteracted by stable network salt-bridges apart from favorable equal contributions of bridge and background terms. Recruitment of extensive network salt-bridges (46%) with a net contribution of -5.0 kcal mol-1 per salt-bridge, seems to be a halophilic design wherein favorable average contribution of background term (-10 kcal mol-1) exceeds than that of bridge term (-7 kcal mol-1). Interiors of proteins from halophiles are seen to possess relatively higher abundance of charge and polar side chains than that of mesophiles which seems to be satisfied by cooperative network salt-bridges. Overall, our theoretical analyses provide insight into halophilic signature in its specific electrostatic interactions which we hope would help in protein engineering and bioinformatics studies.

Dataset Information

An experimental point of view on hydration/solvation in halophilic proteins.

Publications

An experimental point of view on hydration/solvation in halophilic proteins.

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