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In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
Published on: August 13, 2012
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PDZ-Containing Proteins Targeted by the ACE2 Receptor
Célia Caillet-Saguy1, Nicolas Wolff1
1Unité Récepteurs-Canaux, Institut Pasteur, UMR CNRS 3571, 75015 Paris, France.
Viruses
|November 27, 2021
Summary
Angiotensin-converting enzyme 2 (ACE2) binds SARS-CoV-2. Researchers identified 14 human proteins interacting with ACE2
Area of Science:
- Molecular and Cellular Biology
- Virology
- Neuroscience
Background:
- Angiotensin-converting enzyme 2 (ACE2) is a critical host cell receptor for SARS-CoV-2 entry.
- ACE2 is expressed in various human organs, including the brain.
- ACE2's intracellular C-terminal segment contains a PDZ-binding motif (PBM).
Purpose of the Study:
- To identify the human PDZ specificity profile of the ACE2 PBM.
- To investigate potential interactions between ACE2 and human PDZ-domain containing proteins.
- To explore the role of these interactions in viral entry and potential neurological implications of COVID-19.
Main Methods:
- High-throughput holdup assay.
- Measurement of binding intensities between the ACE2 PBM and the human PDZome.
- Identification of ACE2-binding proteins and their dissociation constants.
Main Results:
- Identified 14 human PDZ binders of ACE2 with dissociation constants ranging from 3 to 81 μM.
- Discovered that proteins involved in protein trafficking, such as NHERF, SHANK, and SNX27, bind to ACE2.
- Found that many identified ACE2 partners, including SHANK and MAST families, are expressed in neuronal cells.
Conclusions:
- ACE2 PDZ/PBM interactions may influence ACE2 internalization and recycling, potentially facilitating viral entry.
- Interactions between ACE2 and neuronal proteins might contribute to the neurological symptoms observed in COVID-19 patients.
- These findings highlight novel molecular mechanisms relevant to SARS-CoV-2 pathogenesis and host-pathogen interactions.
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