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10.1016/j.jbc.2021.100940

http://scihub22266oqcxt.onion/10.1016/j.jbc.2021.100940
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suck abstract from ncbi


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pmid34237302      J+Biol+Chem 2021 ; 297 (2): 100940
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  • Recombinant SARS-CoV-2 envelope protein traffics to the trans-Golgi network following amphipol-mediated delivery into human cells #MMPMID34237302
  • Hutchison JM; Capone R; Luu DD; Shah KH; Hadziselimovic A; Van Horn WD; Sanders CR
  • J Biol Chem 2021[Aug]; 297 (2): 100940 PMID34237302show ga
  • The severe acute respiratory syndrome coronavirus 2 envelope protein (S2-E) is a conserved membrane protein that is important for coronavirus (CoV) assembly and budding. Here, we describe the recombinant expression and purification of S2-E in amphipol-class amphipathic polymer solutions, which solubilize and stabilize membrane proteins, but do not disrupt membranes. We found that amphipol delivery of S2-E to preformed planar bilayers results in spontaneous membrane integration and formation of viroporin cation channels. Amphipol delivery of the S2-E protein to human cells results in plasma membrane integration, followed by retrograde trafficking to the trans-Golgi network and accumulation in swollen perinuclear lysosomal-associated membrane protein 1-positive vesicles, likely lysosomes. CoV envelope proteins have previously been proposed to manipulate the luminal pH of the trans-Golgi network, which serves as an accumulation station for progeny CoV particles prior to cellular egress via lysosomes. Delivery of S2-E to cells will enable chemical biological approaches for future studies of severe acute respiratory syndrome coronavirus 2 pathogenesis and possibly even development of "Trojan horse" antiviral therapies. Finally, this work also establishes a paradigm for amphipol-mediated delivery of membrane proteins to cells.
  • |Cell Membrane/*drug effects/metabolism[MESH]
  • |Coronavirus Envelope Proteins/genetics/*metabolism[MESH]
  • |HeLa Cells[MESH]
  • |Humans[MESH]
  • |Lipid Bilayers/chemistry/metabolism[MESH]
  • |Lysosomes/metabolism[MESH]
  • |Polymers/chemistry/*pharmacology[MESH]
  • |Propylamines/chemistry/*pharmacology[MESH]
  • |Protein Transport[MESH]
  • |Recombinant Proteins/genetics/metabolism[MESH]
  • |Surface-Active Agents/chemistry/*pharmacology[MESH]


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