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.
|Titolo:||Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc?|
|Autori:||Kuwata, K.; Li, H.; Yamada, H.; Legname, G.; Prusiner, S. B.; Akasaka, K.; James, T. L.|
|Data di pubblicazione:||2002|
|Digital Object Identifier (DOI):||10.1021/bi026129y|
|Appare nelle tipologie:||1.1 Journal article|