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10.1126/scisignal.abf1117

http://scihub22266oqcxt.onion/10.1126/scisignal.abf1117
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suck abstract from ncbi


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pmid33436498      Sci+Signal 2021 ; 14 (665): ä
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  • Cytoplasmic short linear motifs in ACE2 and integrin beta(3) link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy #MMPMID33436498
  • Kliche J; Kuss H; Ali M; Ivarsson Y
  • Sci Signal 2021[Jan]; 14 (665): ä PMID33436498show ga
  • 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 beta(3) 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 mu2 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 beta(3) 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.
  • |*Virus Internalization[MESH]
  • |Amino Acid Sequence[MESH]
  • |Angiotensin-Converting Enzyme 2/chemistry/genetics/*physiology[MESH]
  • |Autophagy/physiology[MESH]
  • |COVID-19/*virology[MESH]
  • |Endocytosis/physiology[MESH]
  • |Host Microbial Interactions/genetics/physiology[MESH]
  • |Humans[MESH]
  • |Integrin beta3/chemistry/genetics/*physiology[MESH]
  • |Models, Molecular[MESH]
  • |Pandemics[MESH]
  • |Peptide Fragments/chemistry/genetics/physiology[MESH]
  • |Phosphorylation[MESH]
  • |Protein Binding[MESH]
  • |Protein Interaction Domains and Motifs[MESH]
  • |Protein Sorting Signals/genetics/physiology[MESH]
  • |Receptors, Virus/chemistry/genetics/*physiology[MESH]


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