Rational Design of Crystallization Induced Emission Probes to Detect Amorphous Protein Aggregation in Live Cells

2021 ◽  
Author(s):  
Di Shen ◽  
Wenhan Jin ◽  
Yulong Bai ◽  
Yanan Huang ◽  
Haochen Lyu ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Rational Design ◽  
Live Cells

Rational Design of Crystallization Induced Emission Probes to Detect Amorphous Protein Aggregation in Live Cells

2021 ◽  
Author(s):  
Di Shen ◽  
Wenhan Jin ◽  
Yulong Bai ◽  
Yanan Huang ◽  
Haochen Lyu ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Rational Design ◽  
Live Cells

scholarly journals 4D Imaging of Protein Aggregation in Live Cells

10.3791/50083 ◽  
2013 ◽  
Author(s):  
Rachel Spokoini ◽  
Maya Shamir ◽  
Alma Keness ◽  
Daniel Kaganovich
Keyword(s):  
Protein Aggregation ◽  
Live Cells ◽  
4D Imaging

scholarly journals Catechol-Containing Compounds are a Broad Class of Protein Aggregation Inhibitors: Redox State is a Key Determinant of the Inhibitory Activities

2020 ◽  
Author(s):  
Paul Velander ◽  
Ling Wu ◽  
Sherry B. Hildreth ◽  
Nancy J. Vogelaar ◽  
Biswarup Mukhopadhyay ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Small Molecule ◽  
Rational Design ◽  
Redox State ◽  
Broad Class ◽  
Intrinsically Disordered ◽  
Amyloidogenic Proteins ◽  
Key Factor ◽  
Inhibitory Activities ◽  
Screening Platform

Abstract Background: A range of neurodegenerative and related aging diseases, such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes, are linked to toxic protein aggregation. Yet the mechanisms of protein aggregation inhibition by small molecule inhibitors remain poorly understood, in part because most protein targets of aggregation assembly are partially unfolded or intrinsically disordered, which hinders detailed structural characterization of protein-inhibitor complexes and structural-based mechanistic elucidation. Methods: Herein we employed a small molecule screening approach to identify inhibitors against three prototype amyloidogenic proteins in neurodegeneration and related proteinopathies: amylin, Ab and tau. We further systematically investigated selected class of inhibitors under aerobic and anaerobic conditions to uncover a key determinant of the inhibitory activities.Results: One remarkable class of inhibitors identified from all three parallel screenings against different amyloidogenic proteins was catechol-containing compounds and redox-related quinones/anthraquinones. Further mechanistic studies determined that the redox state of the broad class of catechol-containing compounds is a key determinant of the amyloid inhibitor activities. Conclusion: Our small molecule library screening platform was able to identify a broad class of amyloid inhibitors. Redox was found to be a key factor not only regulating the inhibitory activities but also involving the mechanism of inhibition. The molecular insights we gained not only explain why a large number of catechol-containing natural compounds, often enriched in healthy diet, have anti-neurodegeneration and anti-aging activities, but also could guide the rational design of therapeutic or nutraceutical strategies to target a broad range of neurodegenerative and related aging diseases.

Rational design of an ESIPT-based fluorescent probe for selectively monitoring glutathione in live cells and zebrafish

2020 ◽  
Vol 238 ◽  
pp. 118429 ◽  
Author(s):  
Ya-Long Zheng ◽  
Han-Chen Zhang ◽  
Di-Hua Tian ◽  
De-Chen Duan ◽  
Fang Dai ◽  
...  
Keyword(s):  
Fluorescent Probe ◽  
Rational Design ◽  
Live Cells

Rational design of a lysosomal-targeted ratiometric two-photon fluorescent probe for imaging hydrogen polysulfides in live cells

2020 ◽  
Vol 173 ◽  
pp. 107877 ◽  
Author(s):  
Qingxin Han ◽  
Xuan Liu ◽  
Xuechuan Wang ◽  
Ruojun Yin ◽  
Huie Jiang ◽  
...  
Keyword(s):  
Fluorescent Probe ◽  
Rational Design ◽  
Live Cells ◽  
Two Photon

Characterization and real-time imaging of the FTLD-related protein aggregation induced by amyloidogenic peptides

2015 ◽  
Vol 51 (41) ◽  
pp. 8652-8655 ◽  
Author(s):  
Ruei-Yu He ◽  
Yi-Chen Huang ◽  
Chao-Wei Chiang ◽  
Yu-Ju Tsai ◽  
Ting-Juan Ye ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Real Time ◽  
Live Cells ◽  
Related Protein ◽  
Amyloid Fibers ◽  
Real Time Imaging ◽  
C Terminus ◽  
Amyloidogenic Peptides

Q/N- and G-rich polypeptides from the TDP-43 C-terminus formed amyloid fibers in vitro and induced the aggregation of the transfected TDP-43-EGFP in live cells.

Detecting protein aggregation and interaction in live cells: A guide to number and brightness

Methods ◽  
2018 ◽  
Vol 140-141 ◽  
pp. 172-177 ◽  
Author(s):  
Rory Nolan ◽  
Maro Iliopoulou ◽  
Luis Alvarez ◽  
Sergi Padilla-Parra
Keyword(s):  
Protein Aggregation ◽  
Live Cells

scholarly journals Engineering of a fluorescent chemogenetic reporter with tunable color for advanced live-cell imaging

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hela Benaissa ◽  
Karim Ounoughi ◽  
Isabelle Aujard ◽  
Evelyne Fischer ◽  
Rosette Goïame ◽  
...  
Keyword(s):  
Spectral Properties ◽  
Rational Design ◽  
Imaging Techniques ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Super Resolution ◽  
Visible Spectrum ◽  
Live Cells ◽  
Fluorescent Reporters ◽  
Entire Visible Spectrum

AbstractBiocompatible fluorescent reporters with spectral properties spanning the entire visible spectrum are indispensable tools for imaging the biochemistry of living cells and organisms in real time. Here, we report the engineering of a fluorescent chemogenetic reporter with tunable optical and spectral properties. A collection of fluorogenic chromophores with various electronic properties enables to generate bimolecular fluorescent assemblies that cover the visible spectrum from blue to red using a single protein tag engineered and optimized by directed evolution and rational design. The ability to tune the fluorescence color and properties through simple molecular modulation provides a broad experimental versatility for imaging proteins in live cells, including neurons, and in multicellular organisms, and opens avenues for optimizing Förster resonance energy transfer (FRET) biosensors in live cells. The ability to tune the spectral properties and fluorescence performance enables furthermore to match the specifications and requirements of advanced super-resolution imaging techniques.

scholarly journals A3D Database: Structure-based Protein Aggregation Predictions for the Human Proteome

2021 ◽  
Author(s):  
Aleksandra Elzbieta Badaczewska-Dawid ◽  
Javier Garcia-Pardo ◽  
Aleksander Kuriata ◽  
Jordi Pujols ◽  
Salvador Ventura ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Rational Design ◽  
Structural Information ◽  
Protein Solubility ◽  
Protein Structures ◽  
Human Proteome ◽  
Human Protein ◽  
Database Structure ◽  
Human Disorders ◽  
User Friendly

Motivation: Protein aggregation is associated with highly debilitating human disorders and constitutes a major bottleneck for producing therapeutic proteins. Our knowledge of the human protein structures repertoire has dramatically increased with the recent development of the AlphaFold (AF) deep-learning method. This structural information can be used to understand better protein aggregation properties and the rational design of protein solubility. This article uses the Aggrescan3D (A3D) tool to compute the structure-based aggregation predictions for the human proteome and make the predictions available in a database form. Results: Here, we present the A3D Database, in which we analyze the AF-predicted human protein structures (for over 17 thousand non-membrane proteins) in terms of their aggregation properties using the A3D tool. Each entry of the A3D Database provides a detailed analysis of the structure-based aggregation propensity computed with A3D. The A3D Database implements simple but useful graphical tools for visualizing and interpreting protein structure datasets. We discuss case studies illustrating how the database could be used to analyze physiologically relevant proteins. Furthermore, the database enables testing the influence of user-selected mutations on protein solubility and stability, all integrated into a user-friendly interface. Availability and implementation: A3D Database is freely available at: http://biocomp.chem.uw.edu.pl/A3D2/hproteome

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