Structural Biology

Transmembrane targets

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Science  16 Jul 2021:
Vol. 373, Issue 6552, pp. 292-293
DOI: 10.1126/science.373.6552.292-e

Model for the structure of the putative SARS-CoV-2 transmembrane ion channel dimer ORF3A at 2.1 Å

PHOTO: NAT. STRUCT. MOL. BIOL. 10.1038/S41594-021-00619-0 (2021).

In the battle against COVID-19, attention has focused on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which initiates viral entry into host cells, and on viral proteins directly involved in replication. However, other viral proteins also play a role in pathogenicity and are potential drug targets. Kern et al. focused on ORF3A, a transmembrane protein that is implicated in apoptosis and inhibition of autophagy and may form an ion channel. The authors used electron microscopy to determine the structure of a dimer at 2.1-angstrom resolution. Although a polar cavity extends from the cytoplasm into the membrane, conformational changes would be required to open a conduction pathway across the membrane. In liposomes, SARS-CoV-2 3a has a non selective cation channel activity that is blocked by polycation channel inhibitors.

Nat. Struct. Mol. Biol. 10.1038/s41594-021-00619-0 (2021).

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