Role of the HIV-1 envelope transmembrane domain in intracellular sorting

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.

Role of key amino acids in the transmembrane domain of the Newcastle disease virus fusion protein

“…Intracellular transport along the secretory pathway goes hand in hand with sorting of proteins and lipids (19). Hence, a possible role for 519 and 520 residues without expression and fusion activity is not recognized in the cellular transport and sorting machinery (20,21). These residues have an impact on localization of the protein in the compartment where their function is required.…”

Viral Membrane Fusion and the Transmembrane Domain

“…This transport delay may be due to disrupted contacts of the individual trimer TMs with each other or through disruption of protein-membrane interactions. Further analysis of this region demonstrated that R696 does not confer a strict ER localization on the gp41 protein, despite the presence of charged residues within a TMD being a well-recognized ER localization motif [103]. Therefore, other elements in the HIV Env TMD, including its length, override the potential retention signal.…”

Identification of the endoplasmic reticulum localization sequence and N-glycosylation of matrix metalloproteinase 26

“…1E). Positively charged residues are vital for directing proteins into cell compartments or secretory pathways, [21][22][23] and altering the subcellular localization of a protein by site-directed insertions and/or deletions of positively charged residues in critical regions should be feasible. A multi-sequence alignment of all secretory human MMPs showed that the 88-123 region of MMP-26 is unique among all secretory MMPs (Fig.…”