Type II transmembrane domain hydrophobicity dictates the cotranslational dependence for inversion.
Bottom Line: This places stringent hydrophobicity requirements on transmembrane domains (TMDs) from single-spanning membrane proteins.On examining the single-spanning influenza A membrane proteins, we found that the strict hydrophobicity requirement applies to the N(out)-C(in) HA and M2 TMDs but not the N(in)-C(out) TMDs from the type II membrane protein neuraminidase (NA).To investigate this discrepancy, we analyzed NA TMDs of varying hydrophobicity, followed by increasing polypeptide lengths, in mammalian cells and ER microsomes.
Related in: MedlinePlus
Mentions: Our results thus far indicate that full-length NA with a marginally hydrophobic TMD localizes to the PM, likely because the longer C-tail facilitates inversion and potentially ER targeting. By making smaller increases in the C-tail length after the marginally hydrophobic NA TMD, we observed a stepwise increase in the average PM/IC ratios (Figure 4A). The increase slightly began with a C-tail length of 41 aa, which approximates the length of the ribosomal tunnel (Malkin and Rich, 1967; Blobel and Sabatini, 1970), and increased until a length of 76 aa, which showed a PM/IC profile distribution similar to the full-length construct (TM∆G +1.3NA440aa) in this steady-state assay. These results confirmed that the C-tail length contributes to PM localization of the marginally hydrophobic NA TMD.