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A comprehensive comparison of transmembrane domains reveals organelle-specific properties.

Sharpe HJ, Stevens TJ, Munro S - Cell (2010)

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.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

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Positional Analysis of TMD Hydropathy from Different Organelles in Fungi and Vertebrates(A) The mean hydrophobicity (GES scale) of the residues at each position along the aligned TMDs relative to the cytosolic edge was plotted for the indicated protein sets from fungi. The hydrophobicity values represent the free energy for partitioning from water into a hydrophobic environment, and therefore negative values indicate a preference for the interior of a lipid bilayer. Bars show standard error of mean.(B) The distribution of TMD lengths for fungal organelles. The exoplasmic ends of the TMD were defined using the hydrophobicity scanning algorithm as for the cytosolic ends.(C and D) As for (A) and (B), but for vertebrate proteins.(E and F) As for (C) and (D), but for vertebrate proteins of the apical and basolateral domains of the plasma membrane. The Golgi and total plasma membrane plots from (C) and (D) are included for comparison. The 15 apical and 12 basolateral reference proteins are listed in Table S2.(G) The mean values for the TMD hydrophobic lengths of the indicated organelles shown in (B) and (D). For fungi, the differences between Golgi and TGN, Golgi and plasma membrane (PM), and TGN and PM are statistically significant (p < 10−12, two sample t tests), whereas for vertebrates this was the case for Golgi and TGN and Golgi and PM (p < 10−10) but not TGN and PM.See also Figure S2 for tests of robustness and significance of data.
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fig3: Positional Analysis of TMD Hydropathy from Different Organelles in Fungi and Vertebrates(A) The mean hydrophobicity (GES scale) of the residues at each position along the aligned TMDs relative to the cytosolic edge was plotted for the indicated protein sets from fungi. The hydrophobicity values represent the free energy for partitioning from water into a hydrophobic environment, and therefore negative values indicate a preference for the interior of a lipid bilayer. Bars show standard error of mean.(B) The distribution of TMD lengths for fungal organelles. The exoplasmic ends of the TMD were defined using the hydrophobicity scanning algorithm as for the cytosolic ends.(C and D) As for (A) and (B), but for vertebrate proteins.(E and F) As for (C) and (D), but for vertebrate proteins of the apical and basolateral domains of the plasma membrane. The Golgi and total plasma membrane plots from (C) and (D) are included for comparison. The 15 apical and 12 basolateral reference proteins are listed in Table S2.(G) The mean values for the TMD hydrophobic lengths of the indicated organelles shown in (B) and (D). For fungi, the differences between Golgi and TGN, Golgi and plasma membrane (PM), and TGN and PM are statistically significant (p < 10−12, two sample t tests), whereas for vertebrates this was the case for Golgi and TGN and Golgi and PM (p < 10−10) but not TGN and PM.See also Figure S2 for tests of robustness and significance of data.

Mentions: To quantify trends in hydropathy, the mean hydrophobicity over all the sequences in each dataset was plotted relative to residue position. As noted above, the hydropathy plots for the fungal proteins from the early Golgi and late Golgi were found to be very similar, and so the datasets were combined to form a “Golgi” set (Figure S1 available online). For both fungi and vertebrates, the plasma membrane TMDs were on average hydrophobic for a greater length than those of the ER and Golgi (Figures 3A and 3B). For fungi the hydrophobicity values of the Golgi and plasma membrane TMDs were highly significantly different between positions 16 and 24 (p < 1 × 10−10 from two-sample independent t test, Figure S2A). For vertebrates, the difference between Golgi and plasma membrane TMDs was highly significant for positions 17 to 23 (Figure S2A).


A comprehensive comparison of transmembrane domains reveals organelle-specific properties.

Sharpe HJ, Stevens TJ, Munro S - Cell (2010)

Positional Analysis of TMD Hydropathy from Different Organelles in Fungi and Vertebrates(A) The mean hydrophobicity (GES scale) of the residues at each position along the aligned TMDs relative to the cytosolic edge was plotted for the indicated protein sets from fungi. The hydrophobicity values represent the free energy for partitioning from water into a hydrophobic environment, and therefore negative values indicate a preference for the interior of a lipid bilayer. Bars show standard error of mean.(B) The distribution of TMD lengths for fungal organelles. The exoplasmic ends of the TMD were defined using the hydrophobicity scanning algorithm as for the cytosolic ends.(C and D) As for (A) and (B), but for vertebrate proteins.(E and F) As for (C) and (D), but for vertebrate proteins of the apical and basolateral domains of the plasma membrane. The Golgi and total plasma membrane plots from (C) and (D) are included for comparison. The 15 apical and 12 basolateral reference proteins are listed in Table S2.(G) The mean values for the TMD hydrophobic lengths of the indicated organelles shown in (B) and (D). For fungi, the differences between Golgi and TGN, Golgi and plasma membrane (PM), and TGN and PM are statistically significant (p < 10−12, two sample t tests), whereas for vertebrates this was the case for Golgi and TGN and Golgi and PM (p < 10−10) but not TGN and PM.See also Figure S2 for tests of robustness and significance of data.
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fig3: Positional Analysis of TMD Hydropathy from Different Organelles in Fungi and Vertebrates(A) The mean hydrophobicity (GES scale) of the residues at each position along the aligned TMDs relative to the cytosolic edge was plotted for the indicated protein sets from fungi. The hydrophobicity values represent the free energy for partitioning from water into a hydrophobic environment, and therefore negative values indicate a preference for the interior of a lipid bilayer. Bars show standard error of mean.(B) The distribution of TMD lengths for fungal organelles. The exoplasmic ends of the TMD were defined using the hydrophobicity scanning algorithm as for the cytosolic ends.(C and D) As for (A) and (B), but for vertebrate proteins.(E and F) As for (C) and (D), but for vertebrate proteins of the apical and basolateral domains of the plasma membrane. The Golgi and total plasma membrane plots from (C) and (D) are included for comparison. The 15 apical and 12 basolateral reference proteins are listed in Table S2.(G) The mean values for the TMD hydrophobic lengths of the indicated organelles shown in (B) and (D). For fungi, the differences between Golgi and TGN, Golgi and plasma membrane (PM), and TGN and PM are statistically significant (p < 10−12, two sample t tests), whereas for vertebrates this was the case for Golgi and TGN and Golgi and PM (p < 10−10) but not TGN and PM.See also Figure S2 for tests of robustness and significance of data.
Mentions: To quantify trends in hydropathy, the mean hydrophobicity over all the sequences in each dataset was plotted relative to residue position. As noted above, the hydropathy plots for the fungal proteins from the early Golgi and late Golgi were found to be very similar, and so the datasets were combined to form a “Golgi” set (Figure S1 available online). For both fungi and vertebrates, the plasma membrane TMDs were on average hydrophobic for a greater length than those of the ER and Golgi (Figures 3A and 3B). For fungi the hydrophobicity values of the Golgi and plasma membrane TMDs were highly significantly different between positions 16 and 24 (p < 1 × 10−10 from two-sample independent t test, Figure S2A). For vertebrates, the difference between Golgi and plasma membrane TMDs was highly significant for positions 17 to 23 (Figure S2A).

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.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.

Show MeSH