A crucial step for transformation of the normal cellular isoform of the prion protein (PrP(C)) to the infectious prion protein (PrP(Sc)) is thought to entail a previously uncharacterized intermediate conformer, PrP*, which interacts with a template PrP(Sc) molecule in the conversion process. By carrying out (15)N-(1)H two-dimensional NMR measurements under variable pressure on Syrian hamster prion protein rPrP(90-231), we found a metastable conformer of PrP(C) coexisting at a population of approximately 1% at pH 5.2 and 30 degrees C, in which helices B and C are preferentially disordered. While the identity is still unproven, this observed metastable conformer is most logically PrP* or a closely related precursor. The structural characteristics of this metastable conformer are consistent with available immunological and pathological information about the prion protein.

Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc? / Kuwata, K.; Li, H.; Yamada, H.; Legname, G.; Prusiner, S. B.; Akasaka, K.; James, T. L.. - In: BIOCHEMISTRY. - ISSN 0006-2960. - 41:41(2002), pp. 12277-12283. [10.1021/bi026129y]

Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc?

Legname, G.;
2002-01-01

Abstract

A crucial step for transformation of the normal cellular isoform of the prion protein (PrP(C)) to the infectious prion protein (PrP(Sc)) is thought to entail a previously uncharacterized intermediate conformer, PrP*, which interacts with a template PrP(Sc) molecule in the conversion process. By carrying out (15)N-(1)H two-dimensional NMR measurements under variable pressure on Syrian hamster prion protein rPrP(90-231), we found a metastable conformer of PrP(C) coexisting at a population of approximately 1% at pH 5.2 and 30 degrees C, in which helices B and C are preferentially disordered. While the identity is still unproven, this observed metastable conformer is most logically PrP* or a closely related precursor. The structural characteristics of this metastable conformer are consistent with available immunological and pathological information about the prion protein.
2002
41
41
12277
12283
https://pubs.acs.org/doi/abs/10.1021/bi026129y
Kuwata, K.; Li, H.; Yamada, H.; Legname, G.; Prusiner, S. B.; Akasaka, K.; James, T. L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/11797
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