📄 SARS-coronavirus protein 6 conformations required to impede protein import into the nucleus

The severe acute respiratory syndrome coronavirus (SARS-CoV) genome encodes eight accessory proteins. Accessory protein 6 is a 63-residue amphipathic peptide that accelerates coronavirus infection kinetics in cell culture and in mice. Protein 6 is minimally bifunctional, with an N-terminal lipophilic part implicated in accelerating viral growth and a C-terminal hydrophilic part interfering with general protein import into the nucleus. This interference with nuclear import requires interaction between protein 6 and cellular karyopherins, a process that typically involves nuclear localization signal (NLS) motifs. Here we dissected protein 6 using site-directed mutagenesis and found no evidence for a classical NLS. Furthermore, we found that the C-terminal tail of protein 6 impeded nuclear import only in the context of a lipophilic N-terminus, which could be derived from membrane proteins unrelated to protein 6. These findings are discussed in the context of the proposed protein 6 structure.

keywords 🔗 severe acute (1373) 🔗 syndrome coronavirus (1074) 🔗 nuclear import (4) 🔗 coronavirus infection (270) 🔗 membrane protein (93) 🔗 respiratory syndrome (2004) 🔗 acute respiratory (1734) 🔗 cell culture (240) 🔗 site-directed mutagenesis (23) 🔗 accessory proteins (53)

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