Amyloids in bacterial inclusion bodies

Groot, Natalia Sánchez de; Sabaté, Raimon; Ventura, Salvador

doi:10.1016/j.tibs.2009.03.009

Cited by 130 publications

(116 citation statements)

References 72 publications

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“…As discussed previously, bacterial cells can be useful systems for studying in vivo protein aggregation, providing a biologically relevant environment for the screening of antiaggregation drugs [30]. Because overexpression of A40 and A42 in bacteria entails the formation of…”

Section: Resultsmentioning

confidence: 99%

“…Protein aggregation also occurs during the production of heterologous proteins in prokaryotic systems, giving rise to insoluble protein aggregates, the so-called inclusion bodies (IBs), which limits the application of bacteria for recombinant protein production in the biotechnology industry [29]. Contrary to the initial assumption that IBs consisted of disorderly deposited inactive proteins, the existence of highly ordered amyloid-like structures inside IBs has been recently demonstrated [30][31][32][33]. This has dramatically shifted the consideration of IBs from being regarded as useless "molecular dust-balls" to being considered as an excellent and simple but biologically relevant model to study the mechanisms of amyloid folding and deposition related to conformational diseases.…”

Section: Introductionmentioning

confidence: 99%

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Thioflavin-S Staining of Bacterial Inclusion Bodies for the Fast, Simple, and Inexpensive Screening of Amyloid Aggregation Inhibitors

Pouplana¹,

Espargaró²,

Galdeano³

et al. 2014

CMC

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thioflavin-S Staining of Bacterial Inclusion Bodies for the Fast, Simple, and Inexpensive Screening of Amyloid Aggregation Inhibitors

Pouplana¹,

Espargaró²,

Galdeano³

et al. 2014

CMC

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“…Consequently, a number of applications of possible biotechnological and pharmaceutical significance have been developed that exploit the properties of proteins within IBs (reviewed in (44)). On the other hand, it has been increasingly recognized that bacterial IBs can contain protein molecules with amyloid-like structure (45)(46)(47). The protein Sso AcP has enabled the study of fundamental features of the aggregation process from native-like states, in which protein molecules initially self-assemble into species in which monomers retain their folded topology but subsequently convert into amyloidlike entities (7,21,22,24,(26)(27)(28).…”

Section: Native-like Aggregation Of Sso Acp Can Occur In Vivomentioning

confidence: 99%

Direct Conversion of an Enzyme from Native-like to Amyloid-like Aggregates within Inclusion Bodies

Elia

Cantini

Chiti

et al. 2017

Biophysical Journal

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The acylphosphatase from Sulfolobus solfataricus (Sso AcP) is a globular protein able to aggregate in vitro from a native-like conformational ensemble without the need for a transition across the major unfolding energy barrier. This process leads to the formation of assemblies in which the protein retains its native-like structure, which subsequently convert into amyloid-like aggregates. Here, we investigate the mechanism by which Sso AcP aggregates in vivo to form bacterial inclusion bodies after expression in E. coli. Shortly after the initiation of expression, Sso AcP is incorporated into inclusion bodies as a native-like protein, still exhibiting small but significant enzymatic activity. Additional experiments revealed that this overall process of aggregation is enhanced by the presence of the unfolded N-terminal region of the sequence and by destabilization of the globular segment of the protein. At later times, the Sso AcP molecules in the inclusion bodies lose their native-like properties and convert into b-sheet-rich amyloid-like structures, as indicated by their ability to bind thioflavin T and Congo red. These results show that the aggregation behavior of this protein is similar in vivo to that observed in vitro, and that, at least for a predominant part of the protein population, the transition from a native to an amyloid-like structure occurs within the aggregate state.

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“…Different studies showed that amyloidogenic proteins, when expressed in bacteria, form inclusion bodies with common structural and functional features with the highly ordered aggregated amyloids found in the original host species. 24,25 The first characterization of the amyloid properties of the bacterial IBs formed by a prionic protein was that of the fungal HET-S prion protein. 26 Transmission electron microscopy (TEM) combined with solid-state NMR spectroscopy revealed that E. coli IBs of the HET-s prion forming domain consist of fibrillar structures that are almost identical to the molecular structure of HET-s amyloid fibrils assembled in vitro; and these HET-s IBs also showed prion infectivity when transfected into the natural host.…”

Section: Introductionmentioning

confidence: 99%

Mammalian prion amyloid formation in bacteria

Macedo

Cordeiro

Ventura

2016

Prion

Self Cite

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ABSTRACT. Mammalian prion proteins (PrPs) that cause transmissible spongiform encephalopathies are misfolded conformations of the host cellular PrP. The misfolded form, the scrapie PrP (PrP Sc ), can aggregate into amyloid fibrils that progressively accumulate in the brain, evolving to a pathological phenotype. A particular characteristic of PrP Sc is to be found as different strains, related to the diversity of conformational states it can adopt. Prion strains are responsible for the multiple phenotypes observed in prion diseases, presenting different incubation times and diverse deposition profiles in the brain. PrP biochemical properties are also strain-dependent, such as different digestion pattern after proteolysis and different stability. Although they have long been studied, strain formation is still a major unsolved issue in prion biology. The recreation of strainspecific conformational features is of fundamental importance to study this unique pathogenic phenomenon. In our recent paper, we described that murine PrP, when expressed in bacteria, forms amyloid inclusion bodies that possess different strain-like characteristics, depending on the PrP construct. Here, we present an extra-view of these data and propose that bacteria might become a successful model to generate preparative amounts of prion strain-specific assemblies for highresolution structural analysis as well as for addressing the determinants of infectivity and transmissibility.

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Amyloids in bacterial inclusion bodies

Cited by 130 publications

References 72 publications

Thioflavin-S Staining of Bacterial Inclusion Bodies for the Fast, Simple, and Inexpensive Screening of Amyloid Aggregation Inhibitors

Thioflavin-S Staining of Bacterial Inclusion Bodies for the Fast, Simple, and Inexpensive Screening of Amyloid Aggregation Inhibitors

Direct Conversion of an Enzyme from Native-like to Amyloid-like Aggregates within Inclusion Bodies

Mammalian prion amyloid formation in bacteria

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