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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Autores principales:	Célia Caillet-Saguy, Nicolas Wolff
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SARS-CoV-2 ACE2 host factors binding assay PDZ domain Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/67ddec0a259c47b18b633cbb9b97b69c
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spelling	oai:doaj.org-article:67ddec0a259c47b18b633cbb9b97b69c2021-11-25T19:14:07ZPDZ-Containing Proteins Targeted by the ACE2 Receptor10.3390/v131122811999-4915https://doaj.org/article/67ddec0a259c47b18b633cbb9b97b69c2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2281https://doaj.org/toc/1999-4915Angiotensin-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.Célia Caillet-SaguyNicolas WolffMDPI AGarticleSARS-CoV-2ACE2host factorsbinding assayPDZ domainMicrobiologyQR1-502ENViruses, Vol 13, Iss 2281, p 2281 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 ACE2 host factors binding assay PDZ domain Microbiology QR1-502
spellingShingle	SARS-CoV-2 ACE2 host factors binding assay PDZ domain Microbiology QR1-502 Célia Caillet-Saguy Nicolas Wolff PDZ-Containing Proteins Targeted by the ACE2 Receptor
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.
format	article
author	Célia Caillet-Saguy Nicolas Wolff
author_facet	Célia Caillet-Saguy Nicolas Wolff
author_sort	Célia Caillet-Saguy
title	PDZ-Containing Proteins Targeted by the ACE2 Receptor
title_short	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_sort	pdz-containing proteins targeted by the ace2 receptor
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/67ddec0a259c47b18b633cbb9b97b69c
work_keys_str_mv	AT celiacailletsaguy pdzcontainingproteinstargetedbytheace2receptor AT nicolaswolff pdzcontainingproteinstargetedbytheace2receptor
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PDZ-Containing Proteins Targeted by the ACE2 Receptor

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