Abstract
Background The HIV-1 Vpr protein is a 14 kDa accessory protein, required for efficient replication in macrophages. Vpr is incorporated into HIV virions, believed to participate in the docking of the HIV-1 pre-integration complex to the nucleus and to facilitate it’s transport through the nuclear pore. By inducing G2 arrest, Vpr favors transcription from the HIV-1 LTR, which it also transactivates. We noticed two N-terminal amino acids of the HIV-1, SIVmac and SIVcpz Vpr proteins are fully conserved. This N-terminal motif is predicted to be a NatB substrate motif (i.e., Met-Glu-), expected to lead to full Nt-acetylation of the protein, but it also allows the conservation of the Kozak consensus sequence (A/GCCAUGG), critical for efficient protein translation. Nt-acetylation is one of the most common protein modifications in eukaryotes and is believed to affect protein stability, degradation and function.
Highlights
The HIV-1 Vpr protein is a 14 kDa accessory protein, required for efficient replication in macrophages
Nt-acetylation of Vpr was detected by COFRADIC (Combined FRActional Diagonal Chromatography) in HIV-1 infected Jurkat cells, and confirmed with selected reaction monitoring mass spectrometry on transfected cells
We showed full Nt-acetylation of Vpr by COFRADIC in infected Jurkat cells and set out to determine whether Vpr’s amino-terminal sequence is conserved for functional Nt-acetylation, or to allow optimal protein translation
Summary
The HIV-1 Vpr protein is a 14 kDa accessory protein, required for efficient replication in macrophages. Vpr is incorporated into HIV virions, believed to participate in the docking of the HIV-1 pre-integration complex to the nucleus and to facilitate it’s transport through the nuclear pore. By inducing G2 arrest, Vpr favors transcription from the HIV-1 LTR, which it transactivates. We noticed two N-terminal amino acids of the HIV-1, SIVmac and SIVcpz Vpr proteins are fully conserved. This N-terminal motif is predicted to be a NatB substrate motif (i.e., Met-Glu-), expected to lead to full Nt-acetylation of the protein, but it allows the conservation of the Kozak consensus sequence (A/GCCAUGG), critical for efficient protein translation. Nt-acetylation is one of the most common protein modifications in eukaryotes and is believed to affect protein stability, degradation and function
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