Water and molecular chaperones act as weak links of protein folding networks: Energy landscape and punctuated equilibrium changes point towards a game theory of proteins

Kovács, I.; Szalay, Máté; Csermely, Péter

doi:10.1016/j.febslet.2005.03.056

Cited by 57 publications

(63 citation statements)

References 56 publications

(133 reference statements)

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“…Nevertheless, some ideas in that direction have been put forward (most of them for biophysical applications, though). For example, Kovács et al [55] suggested that the binding of two proteins to give a protein complex can be regarded as a "game" in which both proteins have two possible strategies. Elaborating on their ideas, one could imagine that each of the proteins can be either flexible or rigid.…”

Section: Game Theory and Biophysicsmentioning

confidence: 99%

Use of Game-Theoretical Methods in Biochemistry and Biophysics

et al. 2008

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Evolutionary game theory can be considered as an extension of the theory of evolutionary optimisation in that two or more organisms (or more generally, units of replication) tend to optimise their properties in an interdependent way. Thus, the outcome of the strategy adopted by one species (e.g., as a result of mutation and selection) depends on the strategy adopted by the other species. In this review, the use of evolutionary game theory for analysing biochemical and biophysical systems is discussed. The presentation is illustrated by a number of instructive examples such as the competition between microorganisms using different metabolic pathways for adenosine triphosphate production, the secretion of extracellular enzymes, the growth of trees and photosynthesis. These examples show that, due to conflicts of interest, the global optimum (in the sense of being the best solution for the whole system) is not always obtained. For example, some yeast species use metabolic pathways that waste nutrients, and in a dense tree canopy, trees grow taller than would be optimal for biomass productivity. From the viewpoint of game theory, the examples considered can be described by the Prisoner's Dilemma, snowdrift game, Tragedy of the Commons and rock-scissors-paper game.

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Section: Game Theory and Biophysicsmentioning

confidence: 99%

Use of Game-Theoretical Methods in Biochemistry and Biophysics

et al. 2008

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“…However, members of this Hsp family are constitutively present in cells. The induced and the constitutively expressed Hsp families are well known as molecular chaperones which help in normal folding of various polypeptides, assist misfolded proteins to attain or regain their native states, regulate protein degradation, and help in translocation of proteins to different cellular compartments (Hartl and Hayer-Hartl 2002;Kovacs et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Caloric stress alters fat characteristics and Hsp70 expression in milk somatic cells of lactating beef cows

Eitam

Brosh²,

Orlov³

et al. 2009

Cell Stress and Chaperones

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Selection for higher production rate in cattle inhabiting challenging habitats may be considered disadvantageous because of possible deleterious effects on immunity and reproduction and, consequently, on calf crop percentage. In Israel, free-grazing high productive beef cows experience reduction in nutritional quality of forage during up to 8 months of the year. As milk production by dams dictates calf performance, dam's nutritional needs and rebreeding rates, the aim of the present study was to test how lactating beef cows deal with combined caloric and protein stress both at the productive and self protective levels. For this purpose, we studied the effect of long-term caloric stress on milk characteristics and gene expression of stress and milk components producing proteins. Lactating dams responded to caloric stress by decreased body weight, milk, and milk protein production. To compensate for total energy loses in milk, they produced milk of higher fat concentration and shifted the proportions of its fatty acids towards long and unsaturated ones. This was reflected by increased mRNA transcription of the fatty acid binding protein. Prolonged low-energy diet promoted cell-specific heat shock protein (Hsp) response; whereas significant increase of Hsp90 but unchanged levels of Hsp70 proteins were observed in white blood cells, the expression of Hsp70 in milk somatic cells was markedly attenuated, in parallel with a marked increase of α s1 -casein expression. At the mammary gland level, these results may indicate a decrease in turnover of proteins and a shift to an exclusive expression of milk components producing factors. Similar responses to caloric stress were revealed also in ketotic dairy cows. Ketosis promoted a shift towards long and unsaturated fatty acids and an increased expression of α s1 -casein in milk somatic cells. These findings may reflect an evolutionary-preserved mechanism in lactating cows for coping with caloric restriction. Overall, our results provide an index to test suitability of beef cattle breeds to inadequate caloric demands.

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“…Moreover, it is sufficient that these multi-target drugs affect their targets only partially, which corresponds well with the presumed low-affinity interactions of these drugs with several of their targets [16,31,32]. It has been summarized before that weak links (low-probability, low-intensity edges) stabilize complex systems [33,34]. Here we showed a kind of reverse statement: that multiple, weak hits efficiently confuse the integrity of complex systems.…”

Section: Discussionmentioning

confidence: 80%

Multiple weak hits confuse complex systems: A transcriptional regulatory network as an example

Ágoston¹,

2005

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Robust systems, like the molecular networks of living cells are often resistant to single hits such as those caused by high-specificity drugs. Here we show that partial weakening of the Escherichia coli and Saccharomyces cerevisiae transcriptional regulatory networks at a small number (3-5) selected nodes can have a greater impact than the complete elimination of a single selected node. In both cases, the targeted nodes have the greatest possible impact; still the results suggest that in some cases broad specificity compounds or multitarget drug therapies may be more effective than individual high-affinity, highspecificity ones. Multiple but partial attacks mimic well a number of in vivo scenarios and may be useful in the efficient modification of other complex systems.

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Water and molecular chaperones act as weak links of protein folding networks: Energy landscape and punctuated equilibrium changes point towards a game theory of proteins

Cited by 57 publications

References 56 publications

Use of Game-Theoretical Methods in Biochemistry and Biophysics

Use of Game-Theoretical Methods in Biochemistry and Biophysics

Caloric stress alters fat characteristics and Hsp70 expression in milk somatic cells of lactating beef cows

Multiple weak hits confuse complex systems: A transcriptional regulatory network as an example

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