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A conformational switch controlling the toxicity of the prion protein

Frontzek, K; Bardelli, M; Senatore, A; Henzi, A; Reimann, RR; Bedir, S; Marino, M; Hussain, R; Jurt, S; Meisl, G; Pedotti, M; Mazzola, F; Siligardi, G

Prion infections cause conformational changes of the cellular prion protein (PrPC) and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond (‘H-latch’), altering the flexibility of the α2–α3 and β2–α2 loops of PrPC. Expression of a PrP2Cys mutant mimicking the H-latch was constitutively toxic, whereas a PrPR207A mutant unabl...

Date: 2022 | Origin: Repositório Aberto da Universidade do Porto

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