PDZ-containing proteins targeted by the ACE2 receptor

Caillet‐Saguy, Célia; Wolff, Nicolas

doi:10.1101/2021.07.23.453470

Cited by 6 publications

(2 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 C ). Although it is a little weaker than the binding affinity measured by two recent experiments ( K D ≈ 3 and 5 μM, respectively) ( 32 , 37 ), our ITC result is in the normal range of canonical PBM/PDZ interaction (1 μM to 100 μM) ( 19 , 38 – 41 ). Based on previous knowledge, the positions P 3 and P 5 in the PBM should be acidic residues forming an acidic clamp interacting with the conserved residue Arg58 in the PDZ domain of SNX27 and especially the acidic residue at position P -3 is essential for the binding ( 38 ).…”

Section: Resultscontrasting

confidence: 81%

“…Biochemical and Crystallographic Characterization of Interaction between ACE2 and SNX27. During the preparation of our paper, several studies reported the existence of PBM in the C terminus of ACE2 (30,32,36), and it could bind to pairs of PDZcontaining proteins, among which SNX27 is the strongest binder for ACE2/PBM (32,37). Actually, sequence alignment of ACE2 from mammals shows PBM of ACE2 is well conserved and belongs to type I PBM (S/T-X-Ø, where X denotes any residue, and Ø denotes hydrophobic residue) (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry

Yang

Jia

Meng

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

After binding to its cell surface receptor angiotensin converting enzyme 2 (ACE2), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell through directly fusing with plasma membrane (cell surface pathway) or undergoing endocytosis traveling to lysosome/late endosome for membrane fusion (endocytic pathway). However, the endocytic entry regulation by host cell remains elusive. Recent studies show ACE2 possesses a type I PDZ binding motif (PBM) through which it could interact with a PDZ domain-containing protein such as sorting nexin 27 (SNX27). In this study, we determined the ACE2-PBM/SNX27-PDZ complex structure, and, through a series of functional analyses, we found SNX27 plays an important role in regulating the homeostasis of ACE2 receptor. More importantly, we demonstrated SNX27, together with retromer complex (the core component of the endosomal protein sorting machinery), prevents ACE2/virus complex from entering lysosome/late endosome, resulting in decreased viral entry in cells where the endocytic pathway dominates. The ACE2/virus retrieval mediated by SNX27–retromer could be considered as a countermeasure against invasion of ACE2 receptor-using SARS coronaviruses.

show abstract

Section: Resultscontrasting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry

Yang

Jia

Meng

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines

Bellavite¹,

Ferraresi

Isidoro

2023

Biomedicines

View full text Add to dashboard Cite

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses the Spike proteins of its envelope for infecting target cells expressing on the membrane the angiotensin converting enzyme 2 (ACE2) enzyme that acts as a receptor. To control the pandemic, genetically engineered vaccines have been designed for inducing neutralizing antibodies against the Spike proteins. These vaccines do not act like traditional protein-based vaccines, as they deliver the message in the form of mRNA or DNA to host cells that then produce and expose the Spike protein on the membrane (from which it can be shed in soluble form) to alert the immune system. Mass vaccination has brought to light various adverse effects associated with these genetically based vaccines, mainly affecting the circulatory and cardiovascular system. ACE2 is present as membrane-bound on several cell types, including the mucosa of the upper respiratory and of the gastrointestinal tracts, the endothelium, the platelets, and in soluble form in the plasma. The ACE2 enzyme converts the vasoconstrictor angiotensin II into peptides with vasodilator properties. Here we review the pathways for immunization and the molecular mechanisms through which the Spike protein, either from SARS-CoV-2 or encoded by the mRNA-based vaccines, interferes with the Renin-Angiotensin-System governed by ACE2, thus altering the homeostasis of the circulation and of the cardiovascular system. Understanding the molecular interactions of the Spike protein with ACE2 and the consequent impact on cardiovascular system homeostasis will direct the diagnosis and therapy of the vaccine-related adverse effects and provide information for development of a personalized vaccination that considers pathophysiological conditions predisposing to such adverse events.

show abstract

The ACE2 Receptor for Coronavirus Entry Is Localized at Apical Cell—Cell Junctions of Epithelial Cells

Rouaud

Méan

Citi

2022

Cells

View full text Add to dashboard Cite

Transmembrane proteins of adherens and tight junctions are known targets for viruses and bacterial toxins. The coronavirus receptor ACE2 has been localized at the apical surface of epithelial cells, but it is not clear whether ACE2 is localized at apical Cell—Cell junctions and whether it associates with junctional proteins. Here we explored the expression and localization of ACE2 and its association with transmembrane and tight junction proteins in epithelial tissues and cultured cells by data mining, immunoblotting, immunofluorescence microscopy, and co-immunoprecipitation experiments. ACE2 mRNA is abundant in epithelial tissues, where its expression correlates with the expression of the tight junction proteins cingulin and occludin. In cultured epithelial cells ACE2 mRNA is upregulated upon differentiation and ACE2 protein is widely expressed and co-immunoprecipitates with the transmembrane proteins ADAM17 and CD9. We show by immunofluorescence microscopy that ACE2 colocalizes with ADAM17 and CD9 and the tight junction protein cingulin at apical junctions of intestinal (Caco-2), mammary (Eph4) and kidney (mCCD) epithelial cells. These observations identify ACE2, ADAM17 and CD9 as new epithelial junctional transmembrane proteins and suggest that the cytokine-enhanced endocytic internalization of junction-associated protein complexes comprising ACE2 may promote coronavirus entry.

show abstract

PDZ-containing proteins targeted by the ACE2 receptor

Cited by 6 publications

References 49 publications

SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry

SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry

Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines

The ACE2 Receptor for Coronavirus Entry Is Localized at Apical Cell—Cell Junctions of Epithelial Cells

Contact Info

Product

Resources

About