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Mechanisms for stabilisation and the maintenance of solubility in proteins from thermophiles.

Greaves RB, Warwicker J - BMC Struct. Biol. (2007)

Bottom Line: A dataset of 291 thermophile-derived protein structures is compared with mesophile proteins.An exception is increased burial of alanine and proline residues and decreased burial of phenylalanine, methionine, tyrosine and tryptophan in hyperthermophile proteins compared to those from mesophiles.With regard to our observation that aromatic sidechains are less buried in hyperthermophile proteins, further analysis indicates that the placement of some of these groups may facilitate the reduction of folding fluctuations in proteins of the higher growth temperature organisms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester, UK. r.greaves@manchester.ac.uk <r.greaves@manchester.ac.uk>

ABSTRACT

Background: The database of protein structures contains representatives from organisms with a range of growth temperatures. Various properties have been studied in a search for the molecular basis of protein adaptation to higher growth temperature. Charged groups have emerged as key distinguishing factors for proteins from thermophiles and mesophiles.

Results: A dataset of 291 thermophile-derived protein structures is compared with mesophile proteins. Calculations of electrostatic interactions support the importance of charges, but indicate that increases in charge contribution to folded state stabilisation do not generally correlate with the numbers of charged groups. Relative propensities of charged groups vary, such as the substitution of glutamic for aspartic acid sidechains. Calculations suggest an energetic basis, with less dehydration for longer sidechains. Most other properties studied show weak or insignificant separation of proteins from moderate thermophiles or hyperthermophiles and mesophiles, including an estimate of the difference in sidechain rotameric entropy upon protein folding. An exception is increased burial of alanine and proline residues and decreased burial of phenylalanine, methionine, tyrosine and tryptophan in hyperthermophile proteins compared to those from mesophiles.

Conclusion: Since an increase in the number of charged groups for hyperthermophile proteins is separable from charged group contribution to folded state stability, we hypothesise that charged group propensity is important in the context of protein solubility and the prevention of aggregation. Accordingly we find some separation between mesophile and hyperthermophile proteins when looking at the largest surface patch that does not contain a charged sidechain. With regard to our observation that aromatic sidechains are less buried in hyperthermophile proteins, further analysis indicates that the placement of some of these groups may facilitate the reduction of folding fluctuations in proteins of the higher growth temperature organisms.

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Differences within homologous pairs. (a) Correlation between the difference in growth temperature and the difference in GminN for the 102 thermophile-mesophile pairs in the 291 dataset that have an E-value < 10-2. (b) Correlation between the difference in GminN and the difference in StotalN for the 30 hyperthermophile-mesophile pairs in the 67 dataset. Lines of zero ΔStotalN and ΔGminN are marked.
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Figure 10: Differences within homologous pairs. (a) Correlation between the difference in growth temperature and the difference in GminN for the 102 thermophile-mesophile pairs in the 291 dataset that have an E-value < 10-2. (b) Correlation between the difference in GminN and the difference in StotalN for the 30 hyperthermophile-mesophile pairs in the 67 dataset. Lines of zero ΔStotalN and ΔGminN are marked.

Mentions: Analysis of ΔGminN and ΔTgrowth for 102 homologue pairs (pairs from the 291 sets with E-value < 10-2) showed no detailed correlation between these quantities (Figure 10a), despite the moderate separation between hyperthermophile and mesophile protein datasets given by GminN in Figure 2. The result from Figure 2 is evident in the relatively low population of points at higher ΔTgrowth and positive ΔGminN i.e. hyperthermophile proteins generally have lower GminN than mesophile proteins. We presume that since the members of each thermophile-mesophile protein pair in Figure 10a are evolutionarily separated, the many changes in various contributions to protein stabilisation will swamp the overall drift in GminN values.


Mechanisms for stabilisation and the maintenance of solubility in proteins from thermophiles.

Greaves RB, Warwicker J - BMC Struct. Biol. (2007)

Differences within homologous pairs. (a) Correlation between the difference in growth temperature and the difference in GminN for the 102 thermophile-mesophile pairs in the 291 dataset that have an E-value < 10-2. (b) Correlation between the difference in GminN and the difference in StotalN for the 30 hyperthermophile-mesophile pairs in the 67 dataset. Lines of zero ΔStotalN and ΔGminN are marked.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851960&req=5

Figure 10: Differences within homologous pairs. (a) Correlation between the difference in growth temperature and the difference in GminN for the 102 thermophile-mesophile pairs in the 291 dataset that have an E-value < 10-2. (b) Correlation between the difference in GminN and the difference in StotalN for the 30 hyperthermophile-mesophile pairs in the 67 dataset. Lines of zero ΔStotalN and ΔGminN are marked.
Mentions: Analysis of ΔGminN and ΔTgrowth for 102 homologue pairs (pairs from the 291 sets with E-value < 10-2) showed no detailed correlation between these quantities (Figure 10a), despite the moderate separation between hyperthermophile and mesophile protein datasets given by GminN in Figure 2. The result from Figure 2 is evident in the relatively low population of points at higher ΔTgrowth and positive ΔGminN i.e. hyperthermophile proteins generally have lower GminN than mesophile proteins. We presume that since the members of each thermophile-mesophile protein pair in Figure 10a are evolutionarily separated, the many changes in various contributions to protein stabilisation will swamp the overall drift in GminN values.

Bottom Line: A dataset of 291 thermophile-derived protein structures is compared with mesophile proteins.An exception is increased burial of alanine and proline residues and decreased burial of phenylalanine, methionine, tyrosine and tryptophan in hyperthermophile proteins compared to those from mesophiles.With regard to our observation that aromatic sidechains are less buried in hyperthermophile proteins, further analysis indicates that the placement of some of these groups may facilitate the reduction of folding fluctuations in proteins of the higher growth temperature organisms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester, UK. r.greaves@manchester.ac.uk <r.greaves@manchester.ac.uk>

ABSTRACT

Background: The database of protein structures contains representatives from organisms with a range of growth temperatures. Various properties have been studied in a search for the molecular basis of protein adaptation to higher growth temperature. Charged groups have emerged as key distinguishing factors for proteins from thermophiles and mesophiles.

Results: A dataset of 291 thermophile-derived protein structures is compared with mesophile proteins. Calculations of electrostatic interactions support the importance of charges, but indicate that increases in charge contribution to folded state stabilisation do not generally correlate with the numbers of charged groups. Relative propensities of charged groups vary, such as the substitution of glutamic for aspartic acid sidechains. Calculations suggest an energetic basis, with less dehydration for longer sidechains. Most other properties studied show weak or insignificant separation of proteins from moderate thermophiles or hyperthermophiles and mesophiles, including an estimate of the difference in sidechain rotameric entropy upon protein folding. An exception is increased burial of alanine and proline residues and decreased burial of phenylalanine, methionine, tyrosine and tryptophan in hyperthermophile proteins compared to those from mesophiles.

Conclusion: Since an increase in the number of charged groups for hyperthermophile proteins is separable from charged group contribution to folded state stability, we hypothesise that charged group propensity is important in the context of protein solubility and the prevention of aggregation. Accordingly we find some separation between mesophile and hyperthermophile proteins when looking at the largest surface patch that does not contain a charged sidechain. With regard to our observation that aromatic sidechains are less buried in hyperthermophile proteins, further analysis indicates that the placement of some of these groups may facilitate the reduction of folding fluctuations in proteins of the higher growth temperature organisms.

Show MeSH
Related in: MedlinePlus