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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 Residue Size Moment, Related to Figure 5(A and B) The size moment at each position of a protein was defined as being the sum of the vector of the volume of that residue and of the vectors of the volumes of the six residues on either side (i.e., a window of seven residues which approximates to two turns of an α helix—see Experimental Procedures). This moment was calculated at each position for each protein and mean values at each position determined for all the proteins in the same dataset. Glycophorin A dimerizes via a GXXXG motif in its TMD and serves as a positive control. The different datasets from the different organelles do not show large differences in size moment, and hence are not differentially enriched in GXXXG-like dimerization motifs.
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figs3: Positional Analysis of Residue Size Moment, Related to Figure 5(A and B) The size moment at each position of a protein was defined as being the sum of the vector of the volume of that residue and of the vectors of the volumes of the six residues on either side (i.e., a window of seven residues which approximates to two turns of an α helix—see Experimental Procedures). This moment was calculated at each position for each protein and mean values at each position determined for all the proteins in the same dataset. Glycophorin A dimerizes via a GXXXG motif in its TMD and serves as a positive control. The different datasets from the different organelles do not show large differences in size moment, and hence are not differentially enriched in GXXXG-like dimerization motifs.

Mentions: One possible explanation for the reduction in average residue volume in the exoplasmic side of the plasma membrane TMDs is that we were detecting a relative enrichment of GXXXG-like oligomerization motifs. This motif aligns two glycines or other small residues on one face of the helix, and these allow the TMDs to pack closely and dimerize via their backbones (Russ and Engelman, 2000). In order to test if this was the case, we quantified the helical size bias of the TMDs in the different datasets. Residue volume was treated as a vector from the helix, and the values summed for two turns (i.e., seven successive residues) to give a “size moment.” If one side of the helix is flattened, i.e., has more small residues than the opposing side, then the size moment will be higher over that region. Glycophorin A has a GXXXG motif within its TMD and was used as a positive control (Russ and Engelman, 2000). The plasma membrane TMD sets do not show a large peak in size moment in their exoplasmic positions such as that seen for glycophorin A (Figures S3A and S3B). This implies that the exoplasmic parts of the plasma membrane datasets are not substantially enriched in flat dimerization motifs and indicates that the increased proportion of smaller residues instead reflects a difference in overall residue composition all round the transmembrane helix.


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

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

Positional Analysis of Residue Size Moment, Related to Figure 5(A and B) The size moment at each position of a protein was defined as being the sum of the vector of the volume of that residue and of the vectors of the volumes of the six residues on either side (i.e., a window of seven residues which approximates to two turns of an α helix—see Experimental Procedures). This moment was calculated at each position for each protein and mean values at each position determined for all the proteins in the same dataset. Glycophorin A dimerizes via a GXXXG motif in its TMD and serves as a positive control. The different datasets from the different organelles do not show large differences in size moment, and hence are not differentially enriched in GXXXG-like dimerization motifs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2928124&req=5

figs3: Positional Analysis of Residue Size Moment, Related to Figure 5(A and B) The size moment at each position of a protein was defined as being the sum of the vector of the volume of that residue and of the vectors of the volumes of the six residues on either side (i.e., a window of seven residues which approximates to two turns of an α helix—see Experimental Procedures). This moment was calculated at each position for each protein and mean values at each position determined for all the proteins in the same dataset. Glycophorin A dimerizes via a GXXXG motif in its TMD and serves as a positive control. The different datasets from the different organelles do not show large differences in size moment, and hence are not differentially enriched in GXXXG-like dimerization motifs.
Mentions: One possible explanation for the reduction in average residue volume in the exoplasmic side of the plasma membrane TMDs is that we were detecting a relative enrichment of GXXXG-like oligomerization motifs. This motif aligns two glycines or other small residues on one face of the helix, and these allow the TMDs to pack closely and dimerize via their backbones (Russ and Engelman, 2000). In order to test if this was the case, we quantified the helical size bias of the TMDs in the different datasets. Residue volume was treated as a vector from the helix, and the values summed for two turns (i.e., seven successive residues) to give a “size moment.” If one side of the helix is flattened, i.e., has more small residues than the opposing side, then the size moment will be higher over that region. Glycophorin A has a GXXXG motif within its TMD and was used as a positive control (Russ and Engelman, 2000). The plasma membrane TMD sets do not show a large peak in size moment in their exoplasmic positions such as that seen for glycophorin A (Figures S3A and S3B). This implies that the exoplasmic parts of the plasma membrane datasets are not substantially enriched in flat dimerization motifs and indicates that the increased proportion of smaller residues instead reflects a difference in overall residue composition all round the transmembrane helix.

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