Evolution of Protein Structure and Stability in Global Warming

Barik, Sailen

doi:10.3390/ijms21249662

Cited by 16 publications

(6 citation statements)

References 164 publications

(115 reference statements)

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“…In such a gradually changing environment, the network of the interactome, therefore, increased in size and complexity in punctuated steps, reaching equilibrium at each step. This was also suggested previously for the evolution of thermotolerant organisms, selected during global warming [ 153 ].…”

Section: Unanswered Questions and Future Directionssupporting

confidence: 80%

Protein–Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions

Barik¹

2023

IJMS

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The stringent response, originally identified in Escherichia coli as a signal that leads to reprogramming of gene expression under starvation or nutrient deprivation, is now recognized as ubiquitous in all bacteria, and also as part of a broader survival strategy in diverse, other stress conditions. Much of our insight into this phenomenon derives from the role of hyperphosphorylated guanosine derivatives (pppGpp, ppGpp, pGpp; guanosine penta-, tetra- and tri-phosphate, respectively) that are synthesized on starvation cues and act as messengers or alarmones. These molecules, collectively referred to here as (p)ppGpp, orchestrate a complex network of biochemical steps that eventually lead to the repression of stable RNA synthesis, growth, and cell division, while promoting amino acid biosynthesis, survival, persistence, and virulence. In this analytical review, we summarize the mechanism of the major signaling pathways in the stringent response, consisting of the synthesis of the (p)ppGpp, their interaction with RNA polymerase, and diverse factors of macromolecular biosynthesis, leading to differential inhibition and activation of specific promoters. We also briefly touch upon the recently reported stringent-like response in a few eukaryotes, which is a very disparate mechanism involving MESH1 (Metazoan SpoT Homolog 1), a cytosolic NADPH phosphatase. Lastly, using ppGpp as an example, we speculate on possible pathways of simultaneous evolution of alarmones and their multiple targets.

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Section: Unanswered Questions and Future Directionssupporting

confidence: 80%

Protein–Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions

Barik¹

2023

IJMS

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“…A disulfide bond, however, is a strong covalent bond formed between sulfur atoms of two cysteine amino acids. Due to its high bonding energy, disulfide bonds can greatly enhance protein’s tolerance to extreme environments such as heat and acidity and can be found vastly in enzymes of thermophilic species [ 17 , 18 , 19 ]. The introduction of disulfide bonds for enhancing protein stability has been made to a number of enzymes, including formate dehydrogenase [ 20 ], T4 lysozyme [ 21 ], and bacterial alpha-type carbonic anhydrase [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico Analysis of Glucose Oxidase from Aspergillus niger: Potential Cysteine Mutation Sites for Enhancing Protein Stability

Ittisoponpisan

Jeerapan

2021

Bioengineering

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Glucose oxidase (GOx) holds considerable advantages for various applications. Nevertheless, the thermal instability of the enzyme remains a grand challenge, impeding the success in applications outside the well-controlled laboratories, particularly in practical bioelectronics. Many strategies to modify GOx to achieve better thermal stability have been proposed. However, modification of this enzyme by adding extra disulfide bonds is yet to be explored. This work describes the in silico bioengineering of GOx from Aspergillus niger by judiciously analyzing characteristics of disulfide bonds found in the Top8000 protein database, then scanning for amino acid residue pairs that are suitable to be replaced with cysteines in order to establish disulfide bonds. Next, we predicted and assessed the mutant GOx models in terms of disulfide bond quality (bond length and α angles), functional impact by means of residue conservation, and structural impact as indicated by Gibbs free energy. We found eight putative residue pairs that can be engineered to form disulfide bonds. Five of these are located in less conserved regions and, therefore, are unlikely to have a deleterious impact on functionality. Finally, two mutations, Pro149Cys and His158Cys, showed potential for stabilizing the protein structure as confirmed by a structure-based stability analysis tool. The findings in this study highlight the opportunity of using disulfide bond modification as a new alternative technique to enhance the thermal stability of GOx.

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“…[181] For instance, salt bridges can rigidify thermophilic enzymes, [182] and they often have a greater number of hydrophobic core residues and surface charged residues. [183] Protein complexes may similarly be stabilized by a small number of adaptations, such as by formation of disulfide bonds that may even topologically interlink polypeptide chains. [184] Less intuitively, low temperatures are also associated with reduced stability of protein folds, and psychrophilic proteins must be adapted to this.…”

Section: Folding and Protein Assembliesmentioning

confidence: 99%

Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties

Tartwijk

Kaminski

2022

Advanced Biology

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These folds are determined by both protein sequence and solvent properties, and determine protein function. [2] Therefore, the diversity of protein folds in cells allows them to carry out a range of functions, such as catalysis of different reactions. Functional versatility within polypeptide chains is further increased through the presence of multiple independently folding sequences, defined as domains, each associated with distinct functions, such as dimerization or responsiveness to a regulator. However, it is now recognized that some proteins do not have defined conformations, or feature domains that are intrinsically disordered (intrinsically disordered regions, IDRs), and that these confer function by mediating context-dependent proteinprotein interactions. [3] The concept of self-organization of proteins is also applied to assemblies of multiple proteins, in which case it refers to formation of dynamic multi-component structures, [4] including certain oligomeric complexes, filaments, and phase-separated assemblies. In phase-separated assemblies, of which a range exist, IDR-containing proteins form a dense phase within the cytoplasm, commonly referred to as biomolecular condensates. [5] As for folds, the formation of these assemblies depends both on interactions between the phase-separating proteins, which can be mediated by their IDRs, and between these proteins and the surrounding solution. Within the cytoplasm, these phase-separated "droplets" commonly contain RNA, in which case they are referred to as ribonucleoprotein (RNP) granules. They can be considered to have "emergent properties:" certain characteristics can be ascribed to assemblies that are not properties of individual constituent proteins. [6] For instance, biomolecular condensates can display liquid-like properties such as fusion and wetting, which led to their identification as phase-separated droplets. [7] These properties allow them to function as dynamic membraneless organelles, or compartments. This compartmentalization is commonly referred to as occurring on the "mesoscale," which is defined as that range of lengths larger than the size of individual molecular machinery such as ribosomes, but smaller than that of the whole cell. [8] The sensitivity of protein folds and macromolecular interactions to local environmental conditions confers both regulatory potential and risk of loss of function in "extreme" conditions. This regulatory potential is exemplified by and has beenThe cytoplasm is an aqueous, highly crowded solution of active macromolecules. Its properties influence the behavior of proteins, including their folding, motion, and interactions. In particular, proteins in the cytoplasm can interact to form phase-separated assemblies, so-called biomolecular condensates. The interplay between cytoplasmic properties and protein condensation is critical in a number of functional contexts and is the subject of this review. The authors first describe how cytoplasmic properties can affect protein behavior, in particular condensate formation...

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Evolution of Protein Structure and Stability in Global Warming

Cited by 16 publications

References 164 publications

Protein–Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions

Protein–Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions

In Silico Analysis of Glucose Oxidase from Aspergillus niger: Potential Cysteine Mutation Sites for Enhancing Protein Stability

Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties

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