PDZ-Containing Proteins Targeted by the ACE2 Receptor
Angiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brai...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/11/2281 |
| _version_ | 1797508208011509760 |
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| author | Célia Caillet-Saguy Nicolas Wolff |
| author_facet | Célia Caillet-Saguy Nicolas Wolff |
| author_sort | Célia Caillet-Saguy |
| collection | DOAJ |
| description | Angiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brain. ACE2 is a type I membrane protein with an extracellular N-terminal peptidase domain and a C-terminal collectrin-like domain that ends with a single transmembrane helix and an intracellular 44-residue segment. This C-terminal segment contains a PDZ-binding motif (PBM) targeting protein-interacting domains called PSD-95/Dlg/ZO-1 (PDZ). Here, we identified the human PDZ specificity profile of the ACE2 PBM using the high-throughput holdup assay and measuring the binding intensities of the PBM of ACE2 against the full human PDZome. We discovered 14 human PDZ binders of ACE2 showing significant binding with dissociation constants’ values ranging from 3 to 81 μM. NHERF, SHANK, and SNX27 proteins found in this study are involved in protein trafficking. The PDZ/PBM interactions with ACE2 could play a role in ACE2 internalization and recycling that could be of benefit for the virus entry. Interestingly, most of the ACE2 partners we identified are expressed in neuronal cells, such as SHANK and MAST families, and modifications of the interactions between ACE2 and these neuronal proteins may be involved in the neurological symptoms of COVID-19. |
| first_indexed | 2024-03-10T04:59:09Z |
| format | Article |
| id | doaj.art-67ddec0a259c47b18b633cbb9b97b69c |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T04:59:09Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-67ddec0a259c47b18b633cbb9b97b69c2023-11-23T01:58:06ZengMDPI AGViruses1999-49152021-11-011311228110.3390/v13112281PDZ-Containing Proteins Targeted by the ACE2 ReceptorCélia Caillet-Saguy0Nicolas Wolff1Unité Récepteurs-Canaux, Institut Pasteur, UMR CNRS 3571, 75015 Paris, FranceUnité Récepteurs-Canaux, Institut Pasteur, UMR CNRS 3571, 75015 Paris, FranceAngiotensin-converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. Indeed, the first step in viral entry is the binding of the viral trimeric spike (S) protein to ACE2. Abundantly present in human epithelial cells of many organs, ACE2 is also expressed in the human brain. ACE2 is a type I membrane protein with an extracellular N-terminal peptidase domain and a C-terminal collectrin-like domain that ends with a single transmembrane helix and an intracellular 44-residue segment. This C-terminal segment contains a PDZ-binding motif (PBM) targeting protein-interacting domains called PSD-95/Dlg/ZO-1 (PDZ). Here, we identified the human PDZ specificity profile of the ACE2 PBM using the high-throughput holdup assay and measuring the binding intensities of the PBM of ACE2 against the full human PDZome. We discovered 14 human PDZ binders of ACE2 showing significant binding with dissociation constants’ values ranging from 3 to 81 μM. NHERF, SHANK, and SNX27 proteins found in this study are involved in protein trafficking. The PDZ/PBM interactions with ACE2 could play a role in ACE2 internalization and recycling that could be of benefit for the virus entry. Interestingly, most of the ACE2 partners we identified are expressed in neuronal cells, such as SHANK and MAST families, and modifications of the interactions between ACE2 and these neuronal proteins may be involved in the neurological symptoms of COVID-19.https://www.mdpi.com/1999-4915/13/11/2281SARS-CoV-2ACE2host factorsbinding assayPDZ domain |
| spellingShingle | Célia Caillet-Saguy Nicolas Wolff PDZ-Containing Proteins Targeted by the ACE2 Receptor Viruses SARS-CoV-2 ACE2 host factors binding assay PDZ domain |
| title | PDZ-Containing Proteins Targeted by the ACE2 Receptor |
| title_full | PDZ-Containing Proteins Targeted by the ACE2 Receptor |
| title_fullStr | PDZ-Containing Proteins Targeted by the ACE2 Receptor |
| title_full_unstemmed | PDZ-Containing Proteins Targeted by the ACE2 Receptor |
| title_short | PDZ-Containing Proteins Targeted by the ACE2 Receptor |
| title_sort | pdz containing proteins targeted by the ace2 receptor |
| topic | SARS-CoV-2 ACE2 host factors binding assay PDZ domain |
| url | https://www.mdpi.com/1999-4915/13/11/2281 |
| work_keys_str_mv | AT celiacailletsaguy pdzcontainingproteinstargetedbytheace2receptor AT nicolaswolff pdzcontainingproteinstargetedbytheace2receptor |