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.
Hussain
Snawar
S
Department of Microbiology and Immunology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
Gallagher
Tom
T
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism*; D019913:Nuclear Localization Signals; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*
D028884:Karyopherins; D050505:Mutant Proteins; D019913:Nuclear Localization Signals; D014764:Viral Proteins; C507223:protein 6, SARS virus
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