
@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 {5240,
	title = {Microsecond rearrangements of hydrophobic clusters in an initially collapsed globule prime structure formation during the folding of a small protein.},
	journal = {J Mol Biol},
	year = {2016},
	month = {2016 Jun 28},
	abstract = {<p>To determine how polypeptide chain collapse initiates structure formation during protein folding is a long standing goal. It has been challenging to characterize experimentally the dynamics of the polypeptide chain which lead to the formation of a compact kinetic molten globule (MG) in about a millisecond. In this study, the sub-millisecond events that occur early during the folding of monellin (MNEI) from the guanidine hydrochloride-unfolded state have been characterized using multiple fluorescence and fluorescence resonance energy transfer probes. The kinetic MG is shown to form in a non-cooperative manner from the unfolded (U) state as a result of at least three different processes happening during the first millisecond of folding. Initial chain compaction completes within the first 37μs, and further compaction occurs only after structure formation commences at a few milliseconds of folding. Transient non-native and native-like hydrophobic clusters with side-chains of certain residues buried form during the initial chain collapse, and the non-native clusters quickly disassemble. Subsequently, partial chain-desolvation occurs, leading to the formation of a kinetic MG. The initial chain compaction and subsequent chain rearrangement appear to be barrier-less processes. The two structural rearrangements within the collapsed globule appear to prime the protein for the actual folding transition.</p>
},
	issn = {1089-8638},
	doi = {10.1016/j.jmb.2016.06.015},
	author = {Goluguri, Rama Reddy and Udgaonkar, Jayant B}
}
