
@article {56657,
	title = {Microsecond sub-domain motions and the folding and misfolding of the mouse prion protein.},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Apr 26},
	abstract = {<p>Protein aggregation appear 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.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.44766},
	author = {Goluguri, Rama Reddy and Sen, Sreemantee and Udgaonkar, Jayant}
}
@article {60327,
	title = {Monitoring site-specific conformational changes in real-time reveals a misfolding mechanism of the prion protein.},
	journal = {Elife},
	volume = {8},
	year = {2019},
	month = {2019 Jun 24},
	abstract = {<p>During pathological aggregation, proteins undergo remarkable conformational re-arrangements to anomalously assemble into a heterogeneous collection of misfolded multimers, ranging from soluble oligomers to insoluble amyloid fibrils. Inspired by fluorescence resonance energy transfer (FRET) measurements of protein folding, an experimental strategy to study site-specific misfolding kinetics during aggregation, by effectively suppressing contributions from inter-molecular FRET, is described. Specifically, the kinetics of conformational changes across different secondary and tertiary structural segments of the mouse prion protein (moPrP) were monitored independently, after the monomeric units transformed into large oligomers O, which subsequently disaggregated reversibly into small oligomers O at pH 4. The sequence segments spanning helices α2 and α3 underwent a compaction during the formation of O and elongation into β-sheets during the formation of O. The β1-α1-β2 and α2-α3 subdomains were separated, and the helix α1 was unfolded to varying extents in both O and O.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.44698},
	author = {Sengupta, Ishita and Udgaonkar, Jayant}
}
