Effects of spike proteins on angiotensin converting enzyme 2 (ACE2).

Autor: Bejoy J; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Williams CI; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Cole HJ; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Manzoor S; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Davoodi P; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Battaile JI; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Kaushik A; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Nikolaienko SI; Department of Pathological Anatomy, Bogomolets National Medical University, Kyiv, 01601, Ukraine., Brelidze TI; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA., Gychka SG; Department of Pathological Anatomy, Bogomolets National Medical University, Kyiv, 01601, Ukraine., Suzuki YJ; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington DC, 20007, USA. Electronic address: ys82@georgetown.edu.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2023 Oct 15; Vol. 748, pp. 109769. Date of Electronic Publication: 2023 Sep 27.
DOI: 10.1016/j.abb.2023.109769
Abstrakt: The Coronavirus Disease 2019 (COVID-19) pandemic was caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enters host cells through interactions of its spike protein to Angiotensin-Converting Enzyme 2 (ACE2). ACE2 is a peptidase that cleaves Angiotensin II, a critical pathological mediator. This study investigated if the spike protein binding to ACE2 compromises its peptidase activity. Spike/ACE2 Binding Assays suggested that spike proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, but not HKU1, bind to ACE2. S1 and receptor-binding domain (RBD), but not S2, extracellular domain (ECD) or CendR domain, bind to ACE2. While glycosylated spike proteins prepared in HEK293 cells bind to ACE2, non-glycosylated proteins produced in E. coli do not. Cysteine residues of the spike protein expressed in HEK293 cells are fully oxidized, while those of the protein expressed in E. coli are reduced. The deglycosylation of HEK cell-produced protein attenuates the ACE2 binding, while the oxidation of the E. coli protein does not promote the binding. The S1 protein of SARS-CoV-2 enhances the ACE2 peptidase activity, while SARS-CoV, MERS-CoV or HKU1 does not. The ACE2 activity is enhanced by RBD, but not ECD or CendR. In contrast to distinct ACE2 binding capacities of proteins expressed in HEK293 cells and in E. coli, spike proteins expressed in both systems enhance the ACE2 activity. Thus, the spike protein of SARS-CoV-2, but not other coronaviruses, enhances the ACE2 peptidase activity through its RBD in a glycosylation-independent manner.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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