Different packing of external residues can explain differences in the thermostability of proteins from thermophilic and mesophilic organisms

Abstract

Motivation: Understanding the basis of protein stability in thermophilic organisms raises a general question: what structural properties of proteins are responsible for the higher thermostability of proteins from thermophilic organisms compared to proteins from mesophilic organisms? Results: A unique database of 373 structurally well-aligned protein pairs from thermophilic and mesophilic organisms is constructed. Comparison of proteins from thermophilic and mesophilic organisms has shown that the external, water-accessible residues of the first group are more closely packed than those of the second. Packing of interior parts of proteins (residues inaccessible to water molecules) is the same in both cases. The analysis of amino acid composition of external residues of proteins from thermophilic organisms revealed an increased fraction of such amino acids as Lys, Arg and Glu, and a decreased fraction of Ala, Asp, Asn, Gln, Thr, Ser and His. Our theoretical investigation of folding/unfolding behavior confirms the experimental observations that the interactions that differ in thermophilic and mesophilic proteins form only after the passing of the transition state during folding. Thus, different packing of external residues can explain differences in thermostability of proteins from thermophilic and mesophilic organisms. Availability: The database of 373 structurally well-aligned protein pairs is available at

Amino acid contacts in proteins adapted to different temperatures: hydrophobic interactions and surface charges play a key role

“…In the thermophilic proteins, there are a slightly higher number of salt bridges among exposed residues, but the change does not give a P value below our cutoff, and this is only a marginal effect compared to the increase and decrease of other types of contacts. Recently, Glyakina et al (2007) found a higher number of salt bridges in thermophilic proteins, but although the change was statistically significant, the difference between mesophiles and thermophiles was not huge. It seems reasonable that salt bridges plays a positive but not decisive role in thermostabilisation, and cannot explain the higher number of charged residues on the surface or the fact that positively charged residues are increasing much more than negatively charged residues.…”

“…Along a different approach, the loss of long-range contacts has been reported to affect the cooperativity of the folding of hen egg white lysozyme (Dumoulin et al 2005;Zhou et al 2007). These and other studies indicate that there is a link between contacts and cooperativity in protein folding (Abkevich et al 1995;Glyakina et al 2007). For thermophiles that need to retain a well-defined structure at high temperatures, very cooperative folding with a high barrier separating the folded and unfolded state would be advantageous.…”

Comparative genomic analysis of the thermophilic biomass-degrading fungi Myceliophthora thermophila and Thielavia terrestris

“…Among thermophilic fungi, M. thermophila and T. terrestris are two of the best characterized in 9 terms of thermostable enzymes and cellulolytic activity [1][2][3][4] . The fermentation characteristics of 10 these two organisms have been examined and found to be suitable for large-scale production 5,6 .…”

“…Enzymes from thermophilic fungi often 27 tolerate higher temperatures than enzymes from mesophilic species, and some show stability at 28 70-80 °C 1,2 . Notably, it has been reported the cellulolytic activity of some thermophilic species 29 was several times higher than that of the most active cellulolytic mesophiles 3 . Furthermore, 30 biomass-degrading enzymes from thermophilic fungi consistently demonstrate higher hydrolytic 31 capacity 4 despite the fact that extracellular enzyme titers (in grams per liter) are typically lower 1 than those from more conventionally used species such as Trichoderma or Aspergillus.…”

“…6). The fact that these organisms have maintained a diverse array of GH61 genes throughout 3 their evolution intimates their importance for degradation of plant cell wall polysaccharides, with 4 differing GH61 types possibly acting on assorted substrates and/or possessing varied 5 biochemical properties. Differential expression of discrete GH61 subtypes (noted below) 6 supports this view.…”