@article{bb142ad5b17048f3ae12106f78dc968e,
title = "Modulation of Fluorescent Protein Chromophores to Detect Protein Aggregation with Turn-On Fluorescence",
abstract = "We present a fluorogenic method to visualize misfolding and aggregation of a specific protein-of-interest in live cells using structurally modulated fluorescent protein chromophores. Combining photophysical analysis, X-ray crystallography, and theoretical calculation, we show that fluorescence is triggered by inhibition of twisted-intramolecular charge transfer of these fluorophores in the rigid microenvironment of viscous solvent or protein aggregates. Bioorthogonal conjugation of the fluorophore to Halo-tag fused protein-of-interests allows for fluorogenic detection of both misfolded and aggregated species in live cells. Unlike other methods, our method is capable of detecting previously invisible misfolded soluble proteins. This work provides the first application of fluorescent protein chromophores to detect protein conformational collapse in live cells.",
author = "Yu Liu and Wolstenholme, {Charles H.} and Carter, {Gregory C.} and Hongbin Liu and Hang Hu and Grainger, {Leeann S.} and Kun Miao and Matthew Fares and Hoelzel, {Conner A.} and Yennawar, {Hemant P.} and Gang Ning and Manyu Du and Lu Bai and Xiaosong Li and Xin Zhang",
note = "Funding Information: We thank Penn State Microscopy and Cytometry Facility for confocal and electron microscopy images acquisition. Crystal structure of 3 was acquired at the Penn State X-ray crystallography facility. Computational work was supported by National Science Foundation (Grant CHE-1565520 to X.L.) and facilitated via the use of advanced computational, storage, and networking infrastructure provided by the Hyak supercomputer system and funded by the STF at the University of Washington. This work was supported by the Burroughs Wellcome Fund Career Award at the Scientific Interface (X.Z.), Paul Berg Early Career Professorship (X.Z.), Lloyd and Dottie Huck Early Career Award (X.Z.), and National Institutes of Health R01 GM121858 (L.B.). Funding Information: Computational work was supported by National Science Foundation (Grant CHE-1565520 to X.L.) and facilitated via the use of advanced computational, storage, and networking infrastructure provided by the Hyak supercomputer system and funded by the STF at the University of Washington. This work was supported by the Burroughs Wellcome Fund Career Award at the Scientific Interface (X.Z.), Paul Berg Early Career Professorship (X.Z.), Lloyd and Dottie Huck Early Career Award (X.Z.) and National Institutes of Health R01 GM121858 (L.B.). Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2018",
month = jun,
day = "20",
doi = "10.1021/jacs.8b02176",
language = "English (US)",
volume = "140",
pages = "7381--7384",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "24",
}