Back to Search
Start Over
Cytoplasmic short linear motifs in ACE2 and integrin β 3 link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy.
- Source :
-
Science signaling [Sci Signal] 2021 Jan 12; Vol. 14 (665). Date of Electronic Publication: 2021 Jan 12. - Publication Year :
- 2021
-
Abstract
- The spike protein of SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the host cell surface and subsequently enters host cells through receptor-mediated endocytosis. Additional cell receptors may be directly or indirectly involved, including integrins. The cytoplasmic tails of ACE2 and integrins contain several predicted short linear motifs (SLiMs) that may facilitate internalization of the virus as well as its subsequent propagation through processes such as autophagy. Here, we measured the binding affinity of predicted interactions between SLiMs in the cytoplasmic tails of ACE2 and integrin β <subscript>3</subscript> with proteins that mediate endocytic trafficking and autophagy. We validated that a class I PDZ-binding motif mediated binding of ACE2 to the scaffolding proteins SNX27, NHERF3, and SHANK, and that a binding site for the clathrin adaptor AP2 μ2 in ACE2 overlaps with a phospho-dependent binding site for the SH2 domains of Src family tyrosine kinases. Furthermore, we validated that an LC3-interacting region (LIR) in integrin β <subscript>3</subscript> bound to the ATG8 domains of the autophagy receptors MAP1LC3 and GABARAP in a manner enhanced by LIR-adjacent phosphorylation. Our results provide molecular links between cell receptors and mediators of endocytosis and autophagy that may facilitate viral entry and propagation.<br /> (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Amino Acid Sequence
Angiotensin-Converting Enzyme 2 chemistry
Angiotensin-Converting Enzyme 2 genetics
Autophagy physiology
Endocytosis physiology
Host Microbial Interactions genetics
Host Microbial Interactions physiology
Humans
Integrin beta3 chemistry
Integrin beta3 genetics
Models, Molecular
Pandemics
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments physiology
Phosphorylation
Protein Binding
Protein Interaction Domains and Motifs
Protein Sorting Signals genetics
Protein Sorting Signals physiology
Receptors, Virus chemistry
Receptors, Virus genetics
SARS-CoV-2 genetics
Angiotensin-Converting Enzyme 2 physiology
COVID-19 virology
Integrin beta3 physiology
Receptors, Virus physiology
SARS-CoV-2 pathogenicity
SARS-CoV-2 physiology
Virus Internalization
Subjects
Details
- Language :
- English
- ISSN :
- 1937-9145
- Volume :
- 14
- Issue :
- 665
- Database :
- MEDLINE
- Journal :
- Science signaling
- Publication Type :
- Academic Journal
- Accession number :
- 33436498
- Full Text :
- https://doi.org/10.1126/scisignal.abf1117