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|a 10.1016/j.bej.2021.108292
|2 doi
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|a eng
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| 100 |
1 |
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|a Chau, Edward
|e verfasserin
|4 aut
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| 245 |
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|a Engineering of a protein probe with multiple inputs and multiple outputs for evaluation of alpha synuclein aggregation states
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|c 2022
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|a Text
|b txt
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|a ƒaComputermedien
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|a ƒa Online-Ressource
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|a Date Revised 02.01.2023
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|a published: Print-Electronic
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|a Citation Status PubMed-not-MEDLINE
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|a The aggregation of α-synuclein (αS) into oligomers and fibrils is implicated in the pathology of Parkinson's Disease (PD). While a molecular probe for rapid and comprehensive evaluation of αS aggregation states is critical for a better understanding of PD pathology, identification of therapeutic candidates, and the development of early diagnostic strategies, no such probe has yet to be developed. A structurally flexible αS variant, PG65, was previously developed as a target binding-driven, conformation-switching molecular probe for rapid αS oligomer detection. Though informative, detection using PG65 provides no comprehensive assessment of the αS aggregation states. In the present study, we report engineering of a molecular probe, PG65-MIMO (a PG65 variant with Multiple-Inputs and Multiple-Outputs), that rapidly (within 2 hr) produces comprehensive information on αS aggregation states. PG65-MIMO generates distinct fluorescence responses to the three major αS conformers (monomers, oligomers, and fibrils). PG65-MIMO also displays unique fluorescent signals for αS oligomers, depending on the tris(2-carboxyethyl)phosphine (TCEP) concentration. Our results suggest that the TCEP dependent signaling of PG65-MIMO may be associated with its conformational states. Overall, our study illustrates engineering of an αS variant to create a molecular probe for handling multiple inputs and multiple outputs, addressing the technological gap in αS detection
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|a Journal Article
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|a Aggregation
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|a Alpha-synuclein
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|a Amyloid
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| 650 |
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|a Fibril
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| 650 |
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|a Oligomer
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| 650 |
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4 |
|a Protein probe
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| 700 |
1 |
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|a Kim, Jin Ryoun
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Biochemical engineering journal
|d 1998
|g 178(2022) vom: 04. Jan.
|w (DE-627)NLM098270710
|x 1369-703X
|7 nnas
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| 773 |
1 |
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|g volume:178
|g year:2022
|g day:04
|g month:01
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| 856 |
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|u http://dx.doi.org/10.1016/j.bej.2021.108292
|3 Volltext
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