Abstract
BackgroundThe envelope protein of lentiviruses are type I transmembrane proteins, and their transmembrane domain contains conserved potentially charged residues. This highly unusual feature would be expected to cause endoplasmic reticulum (ER) localization. The aim of this study was to determine by which means the HIV-1 Env protein is transported to the cell surface although its transmembrane domain contains a conserved arginine residue.ResultsWe expressed various chimeric proteins and analyzed the influence of their transmembrane domain on their intracellular localization. The transmembrane domain of the HIV-1 Env protein does not cause ER retention. This is not due to the presence of conserved glycine residues, or to the position of the arginine residue, but to the length of the transmembrane domain. A shortened version of the Env transmembrane domain causes arginine-dependent ER targeting. Remarkably, the transmembrane domain of the HIV-1 Env protein, although it does not confer ER retention, interacts efficiently with negatively charged residues in the membrane.ConclusionThese results suggest that the intrinsic properties of the HIV-1 Env transmembrane domain allow the protein to escape ER-retention mechanisms, while maintaining its ability to interact with cellular proteins and to influence cellular physiology.
Highlights
The envelope protein of lentiviruses are type I transmembrane proteins, and their transmembrane domain contains conserved potentially charged residues
Charged residues in the Transmembrane domain (TMD) of lentiviral envelope proteins In almost every sequenced isolate of Humain immunodeficiency virus type I (HIV-1), an arginine residue is positioned in the TMD of the Env protein (Fig. 1)
An arginine or a lysine residue is found in the TMD of the envelope protein of most other lentiviruses, notably HIV-2, simian (SIV) and bovine (BIV) immunodeficiency viruses, caprine arthritis/encephalitis virus (CAEV), Maedi visna ovine pneumonia virus (MVV) and equine infectious anemia virus (EIAV) (Fig. 1)
Summary
The envelope protein of lentiviruses are type I transmembrane proteins, and their transmembrane domain contains conserved potentially charged residues. This highly unusual feature would be expected to cause endoplasmic reticulum (ER) localization. Each individual protein can eventually be found in the ER, in the Golgi apparatus, or at the cell surface. This ensures the proper localization of individual proteins in the compartment where their function is required (e.g. the ER for the signal peptidase, or the surface for the transferrin receptor). It avoids the transport to the cell surface of proteins that are misfolded or incompletely assembled, and participates in the quality control of secreted proteins (reviewed in [1, 2]).
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