Entropic Bristles Tune the Seeding Efficiency of Prion-Nucleating Fragments
| Autor: | Marion Mathelié-Guinlet, Yves F. Dufrêne, Rodrigo Gallardo, Emiel Michiels, Frederic Rousseau, Shu Liu, Ina Vorberg, Joost Schymkowitz, Nikolaos N. Louros |
|---|---|
| Přispěvatelé: | UCL - SST/LIBST - Louvain Institute of Biomolecular Science and Technology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
entropic bristle Amyloid Prions Entropy Green Fluorescent Proteins Saccharomyces cerevisiae Nucleation Sequence (biology) Peptide Genetics and Molecular Biology Protein aggregation Fibril Article General Biochemistry Genetics and Molecular Biology prion 03 medical and health sciences Mice Sup35 0302 clinical medicine brittle Cell Line Tumor Animals metabolism [Peptides] Asparagine ddc:610 lcsh:QH301-705.5 chemistry.chemical_classification biology fibril amyloid biology.organism_classification 3. Good health 030104 developmental biology chemistry lcsh:Biology (General) metabolism [Green Fluorescent Proteins] metabolism [Prions] General Biochemistry Biophysics Peptides 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 30, Iss 8, Pp 2834-2845.e3 (2020) Cell Reports Cell Reports, Vol. 30, no.8, p. 2834-2845.e3 (2020) Cell reports 30(8), 2834-2845.e3 (2020). doi:10.1016/j.celrep.2020.01.098 |
| DOI: | 10.1016/j.celrep.2020.01.098 |
| Popis: | Summary Prions of lower eukaryotes are self-templating protein aggregates with cores formed by parallel in-register beta strands. Short aggregation-prone glutamine (Q)- and asparagine (N)-rich regions embedded in longer disordered domains have been proposed to act as nucleation sites that initiate refolding of soluble prion proteins into highly ordered fibrils, termed amyloid. We demonstrate that a short Q/N-rich peptide corresponding to a proposed nucleation site in the prototype Saccharomyces cerevisiae prion protein Sup35 is sufficient to induce infectious cytosolic prions in mouse neuroblastoma cells ectopically expressing the soluble Sup35 NM prion domain. Embedding this nucleating core in a non-native N-rich sequence that does not form amyloid but acts as an entropic bristle quadruples seeding efficiency. Our data suggest that large disordered sequences flanking an aggregation core in prion proteins act as not only solubilizers of the monomeric protein but also breakers of the formed amyloid fibrils, enhancing infectivity of the prion seeds. Graphical Abstract Highlights • A short peptide derived from Sup35 (p103–113) forms rigid amyloid fibrils • p103–113 fibrils can induce infectious Sup35 NM prions in mammalian cells • Embedding p103–113 in an N-rich sequence increases fibril brittleness • Increased fibril brittleness enhances prion-inducing capacity A protein aggregate can contain infective properties, prions being the prime example. Michiels et al. show that these infective properties are encoded in the specific amino acid sequence flanking the aggregation core of a protein. These so-called entropic bristle sequences drive fiber brittleness, a crucial feature for amyloid infectivity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|