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A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment
Author(s) -
Owyong Tze Cin,
Subedi Pramod,
Deng Jieru,
Hinde Elizabeth,
Paxman Jason J.,
White Jonathan M.,
Chen Weisan,
Heras Begoña,
Wong Wallace W. H.,
Hong Yuning
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201914263
Subject(s) - proteome , polarity (international relations) , proteostasis , cytoplasm , organelle , unfolded protein response , subcellular localization , microbiology and biotechnology , nucleus , biophysics , function (biology) , chemistry , biology , cell , biochemistry , endoplasmic reticulum
Environmental polarity is an important factor that drives biomolecular interactions to regulate cell function. Herein, a general method of using the fluorogenic probe NTPAN‐MI is reported to quantify the subcellular polarity change in response to protein unfolding. NTPAN‐MI fluorescence is selectively activated upon labeling unfolded proteins with exposed thiols, thereby reporting on the extent of proteostasis. NTPAN‐MI also reveals the collapse of the host proteome caused by influenza A virus infection. The emission profile of NTPAN‐MI contains information of the local polarity of the unfolded proteome, which can be resolved through spectral phasor analysis. Under stress conditions that disrupt different checkpoints of protein quality control, distinct patterns of dielectric constant distribution in the cytoplasm can be observed. However, in the nucleus, the unfolded proteome was found to experience a more hydrophilic environment across all the stress conditions, indicating the central role of nucleus in the stress response process.