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Functional amyloidogenesis and cytotoxicity-insights into biology and pathology.

ABSTRACT: Prions are self-templating protein structures that can be transferred from organism to organism. The [Het-s] prion propagates as a functional amyloid aggregate in the filamentous fungi Podospora anserina, and is involved in mediating heterokaryon incompatibility. Fusion of a P. anserina strain harboring the [Het-s] prion with another strain expressing the soluble Het-S protein results in cell death. The mechanism of Het-s/Het-S-mediated cell death has now been revealed in a paper just published in PLOS Biology. The study shows that Het-s and Het-S C-terminal domain co-amyloidogenesis induces a profound conformational rearrangement in the N-terminal Het-S HeLo domain, resulting in the exposure of a nascent transmembrane helix. Oligomerization of these helices leads to pore formation, leakage of the cytosolic contents, and subsequent cell death. Thus, Het-s amyloid plays a major role in the life cycle of P. anserina by orchestrating a complex conformational change in the Het-S protein, resulting in cytotoxicity by compromising membrane integrity. This ability of Het-s functional amyloid to initiate programmed cytotoxicity by mediating a conformational change in another protein significantly expands the functional repertoire of amyloid. Moreover, the mechanism of Het-S cell killing may be similar to the mechanism by which some pathological amyloid proteins lead to the demise of post-mitotic tissue.

SUBMITTER: Fowler DM

PROVIDER: S-EPMC3531510 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Functional amyloidogenesis and cytotoxicity-insights into biology and pathology.

Fowler Douglas M DM Kelly Jeffery W JW

PLoS biology 20121227 12

Prions are self-templating protein structures that can be transferred from organism to organism. The [Het-s] prion propagates as a functional amyloid aggregate in the filamentous fungi Podospora anserina, and is involved in mediating heterokaryon incompatibility. Fusion of a P. anserina strain harboring the [Het-s] prion with another strain expressing the soluble Het-S protein results in cell death. The mechanism of Het-s/Het-S-mediated cell death has now been revealed in a paper just published ...[more]

PMID: 23300381

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Dataset Information

Functional amyloidogenesis and cytotoxicity-insights into biology and pathology.

Publications

Functional amyloidogenesis and cytotoxicity-insights into biology and pathology.

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