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Disruption of endocytosis through chemical inhibition of clathrin heavy chain function
- Source :
- Nature Chemical Biology
- Publication Year :
- 2019
-
Abstract
- Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Moreover, we present a chemically improved ES9 analog, ES9-17, which lacks the undesirable side effects of ES9 while retaining the ability to target CHC. ES9 and ES9-17 have expanded the chemical toolbox used to probe CHC function, and present chemical scaffolds for further design of more specific and potent CHC inhibitors across different systems.
- Subjects :
- Models, Molecular
Arabidopsis
Thiophenes
Endocytosis
Clathrin
03 medical and health sciences
symbols.namesake
Benzene Derivatives
Molecule
Humans
Molecular Biology
030304 developmental biology
0303 health sciences
Heavy chain
biology
Molecular Structure
Chemistry
030302 biochemistry & molecular biology
Cell Biology
Golgi apparatus
biology.organism_classification
Small molecule
Clathrin Heavy Chains
biology.protein
Biophysics
symbols
Function (biology)
Subjects
Details
- ISSN :
- 15524450
- Database :
- OpenAIRE
- Journal :
- Nature Chemical Biology
- Accession number :
- edsair.doi.dedup.....f34ba064e8c7d674e1b7336dd52b6b78
- Full Text :
- https://doi.org/10.1038/s41589-019-0262-1