Protecting activity of desiccated enzymes

Piszkiewicz, Samantha; Gunn, Kathryn H.; Warmuth, Owen; Propst, Ashlee; Mehta, Aakash; Nguyen, Kenny H.; Kuhlman, Elizabeth; Guseman, Alex J.; Stadmiller, Samantha S.; Boothby, Thomas E.; Neher, Saskia B.; Pielak, Gary J.

doi:10.1002/pro.3604

Cited by 60 publications

(155 citation statements)

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“…Both the water replacement and preferential hydration hypotheses require that a protectant be hydrophilic, with the ability to order water, without an extensive internal hydrogen bonding network [ 81 , 83 ]. CAHS proteins have the ability to protect desiccation-sensitive proteins [ 7 , 8 ], and members of this family fall in line with the characteristics needed to conform to these two solvation-based hypotheses [ 25 ]. CAHS proteins are larger than trehalose and other disaccharides, and therefore capable of crowding water to the surface of the client protein.…”

Section: Main Textmentioning

confidence: 99%

“…In this regard, TDPs may provide an interesting evolutionary example of cross-tolerance; when a mediator that has evolved to cope with one stress confers protection to a different stress. CAHS proteins, for example, have been seen to function in vitro to protect proteins from both desiccation and freeze/thaw induced perturbations [ 7 , 8 ]. While freezing, like desiccation, removes solvating water, transcriptome level responses to these two stresses are highly divergent [ 7 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

“…For example, to survive high temperatures or the vacuum of outer space, tardigrades must first be in a desiccated state [ 4 ]. The idea of desiccation as a means of preserving or stabilizing biological material, sometimes referred to as xeroprotection, has been pursued in the biomedical field for decades [ 5 – 8 ]. However, the mechanisms underlying anhydrobiosis remain one of the enduring mysteries of physiology.…”

Section: Introductionmentioning

confidence: 99%

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The biology of tardigrade disordered proteins in extreme stress tolerance

Hesgrove

Boothby

2020

Cell Commun Signal

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Disordered proteins have long been known to help mediate tolerance to different abiotic stresses including freezing, osmotic stress, high temperatures, and desiccation in a diverse set of organisms. Recently, three novel families of intrinsically disordered proteins were identified in tardigrades, microscopic animals capable of surviving a battery of environmental extremes. These three families include the Cytoplasmic-, Secreted-, and Mitochondrial- Abundant Heat Soluble (CAHS, SAHS, and MAHS) proteins, which are collectively termed Tardigrade Disordered Proteins (TDPs). At the level of sequence conservation TDPs are unique to tardigrades, and beyond their high degree of disorder the CAHS, SAHS, and MAHS families do not resemble one another. All three families are either highly expressed constitutively, or significantly enriched in response to desiccation. In vivo, ex vivo, and in vitro experiments indicate functional roles for members of each TDP family in mitigating cellular perturbations induced by various abiotic stresses. What is currently lacking is a comprehensive and holistic understanding of the fundamental mechanisms by which TDPs function, and the properties of TDPs that allow them to function via those mechanisms. A quantitative and systematic approach is needed to identify precisely what cellular damage TDPs work to prevent, what sequence features are important for these functions, and how those sequence features contribute to the underlying mechanisms of protection. Such an approach will inform us not only about these fascinating proteins, but will also provide insights into how the sequence of a disordered protein can dictate its functional, structural, and dynamic properties. Graphical abstract

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Section: Main Textmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The biology of tardigrade disordered proteins in extreme stress tolerance

Hesgrove

Boothby

2020

Cell Commun Signal

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“…Moreover, the role played by EtAHS or CAHS in anhydrobiosis has not been elucidated to date. Few studies have investigated this topic, and they have obtained ambiguous results 49 . Further studies on this subject are also necessary to fully elucidate the molecular mechanisms underlying anhydrobiosis in tardigrades.…”

Section: Discussionmentioning

confidence: 99%

Multiomics study of a heterotardigrade,Echinisicus testudo, suggests convergent evolution of anhydrobiosis-related proteins in Tardigrada

Murai

Yagi-Utsumi

Tomita

et al. 2020

Preprint

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Many limno-terrestrial tardigrades can enter an ametabolic state upon desiccation, in which the animals can withstand extreme environments. To date, studies of the molecular mechanism have predominantly investigated the class Eutardigrada, and that in the Heterotardigrada, remains elusive. To this end, we report a multiomics study of the heterotardigrade Echiniscus testudo, which is one of the most desiccation-tolerant species. None of the previously identified tardigrade-specific anhydrobiosis-related genes was conserved, while the loss and expansion of existing pathways were partly shared. Furthermore, we identified two families of novel abundant heat-soluble proteins and the proteins exhibited structural changes from random coil to α-helix as the water content decreased in vitro. These characteristics are analogous to those of anhydrobiosis-related protein in eutardigrades, while there is no conservation at the sequence level. Our results suggest that Heterotardigrada have partly shared but distinct anhydrobiosis machinery compared with Eutardigrada, possibly due to convergent evolution within Tardigrada.

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“…As new molecular compounds with similar protection characteristics as trehalose are found in tardigrades, similar applications in medical science may be expected. One family of the tardigrade-specific intrinsically-disordered proteins (TDPs), cytosolic abundant heat-soluble (CAHS) proteins, has recently been tested for stabilization of pharmaceutical excipients (lactate dehydrogenase, lipoprotein lipase) with promising results [84].…”

Section: Relevance Of Tardigrade Stress Mechanisms For Research Onmentioning

confidence: 99%

Radiation Tolerance in Tardigrades: Current Knowledge and Potential Applications in Medicine

Jonsson

2019

Cancers

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Tardigrades represent a phylum of very small aquatic animals in which many species have evolved adaptations to survive under extreme environmental conditions, such as desiccation and freezing. Studies on several species have documented that tardigrades also belong to the most radiation-tolerant animals on Earth. This paper gives an overview of our current knowledge on radiation tolerance of tardigrades, with respect to dose-responses, developmental stages, and different radiation sources. The molecular mechanisms behind radiation tolerance in tardigrades are still largely unknown, but omics studies suggest that both mechanisms related to the avoidance of DNA damage and mechanisms of DNA repair are involved. The potential of tardigrades to provide knowledge of importance for medical sciences has long been recognized, but it is not until recently that more apparent evidence of such potential has appeared. Recent studies show that stress-related tardigrade genes may be transfected to human cells and provide increased tolerance to osmotic stress and ionizing radiation. With the recent sequencing of the tardigrade genome, more studies applying tardigrade omics to relevant aspects of human medicine are expected. In particular, the cancer research field has potential to learn from studies on tardigrades about molecular mechanisms evolved to maintain genome integrity.

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Protecting activity of desiccated enzymes

Cited by 60 publications

References 75 publications

The biology of tardigrade disordered proteins in extreme stress tolerance

The biology of tardigrade disordered proteins in extreme stress tolerance

Multiomics study of a heterotardigrade,Echinisicus testudo, suggests convergent evolution of anhydrobiosis-related proteins in Tardigrada

Radiation Tolerance in Tardigrades: Current Knowledge and Potential Applications in Medicine

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