Microsecond sub-domain motions and the folding and misfolding of the mouse prion protein.

Abstract:

:Protein aggregation appears to originate from partially unfolded conformations that are sampled through stochastic fluctuations of the native protein. It has been a challenge to characterize these fluctuations, under native like conditions. Here, the conformational dynamics of the full-length (23-231) mouse prion protein were studied under native conditions, using photoinduced electron transfer coupled to fluorescence correlation spectroscopy (PET-FCS). The slowest fluctuations could be associated with the folding of the unfolded state to an intermediate state, by the use of microsecond mixing experiments. The two faster fluctuations observed by PET-FCS, could be attributed to fluctuations within the native state ensemble. The addition of salt, which is known to initiate the aggregation of the protein, resulted in an enhancement in the time scale of fluctuations in the core of the protein. The results indicate the importance of native state dynamics in initiating the aggregation of proteins.

journal_name

Elife

journal_title

eLife

authors

Goluguri RR,Sen S,Udgaonkar J

doi

10.7554/eLife.44766

subject

Has Abstract

pub_date

2019-04-26 00:00:00

issn

2050-084X

pii

44766

journal_volume

8

pub_type

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