A comprehensive comparison of transmembrane domains reveals organelle-specific properties.
Bottom Line: The various membranes of eukaryotic cells differ in composition, but it is at present unclear if this results in differences in physical properties.In addition, TMDs from post-ER organelles show striking asymmetries in amino acid compositions across the bilayer that is linked to residue size and varies between organelles.The pervasive presence of organelle-specific features among the TMDs of a particular organelle has implications for TMD prediction, regulation of protein activity by location, and sorting of proteins and lipids in the secretory pathway.
Affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.Show MeSH
Mentions: Although the hydrophobic cores of the TMDs from the various organelles differ in length, they all have similar hydropathy values that do not vary greatly along the length of this core. However, the residue frequency plots above suggest that the abundance of individual hydrophobic residues changes along the length of the TMDs (Figure 2). The residues valine, glycine, and leucine are uniformly distributed through the fungal Golgi TMDs, but all are asymmetrically distributed in plasma membrane TMDs, with valine and glycine being favored in more exoplasmic positions, whereas leucine shows the opposite trend (Figures 4A and 4B). To quantify further the degree of residue asymmetry, the relative lengths of each TMD in an organelle set were calculated as above and used to define the halves of the TMD corresponding to the inner and outer leaflets of the membrane. The abundance of each amino acid in the “inner” leaflet was subtracted from the abundance in the “outer” leaflet and divided by the total abundance to give a ratio for the leaflet preference. The mean ratios for each hydrophobic residue in each organelle set are shown in Figures 4C (fungi) and 4D (vertebrates). The values are plotted against the volume of each amino acid residue (Pontius et al., 1996). For fungal plasma membrane proteins, the overall trend is for the outer leaflet half of the TMD to have an increase in smaller residues and decrease in larger residues, with the opposite trend for the Golgi proteins, whereas ER TMDs show no difference in relative abundance of hydrophobic residues between the leaflets. For vertebrates, a comparison of Golgi and plasma membrane asymmetry shows a similar trend to that seen in fungi, albeit smaller in scale. Overall, these results suggest that the constraints on amino acid composition of TMDs differ between the two leaflets of the bilayer.
Affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.