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Principles of membrane protein interactions with annular lipids deduced from aquaporin-0 2D crystals.

Hite RK, Li Z, Walz T - EMBO J. (2010)

Bottom Line: Comparison of the two structures shows that AQP0 does not adapt to the different length of the acyl chains in EPLs and that the distance between the phosphodiester groups in the two leaflets of the DMPC and EPL bilayers is almost identical.The interactions of annular lipids with membrane proteins seem to be driven by the propensity of the acyl chains to fill gaps in the protein surface.Interactions of the lipid headgroups may be responsible for the specific interactions found in tightly bound lipids but seem to have a negligible effect on interactions of generic annular lipids with membrane proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT
We have previously described the interactions of aquaporin-0 (AQP0) with dimyristoyl phosphatidylcholine (DMPC) lipids. We have now determined the 2.5 A structure of AQP0 in two-dimensional (2D) crystals formed with Escherichia coli polar lipids (EPLs), which differ from DMPC both in headgroups and acyl chains. Comparison of the two structures shows that AQP0 does not adapt to the different length of the acyl chains in EPLs and that the distance between the phosphodiester groups in the two leaflets of the DMPC and EPL bilayers is almost identical. The EPL headgroups interact differently with AQP0 than do those of DMPC, but the acyl chains in the EPL and DMPC bilayers occupy similar positions. The interactions of annular lipids with membrane proteins seem to be driven by the propensity of the acyl chains to fill gaps in the protein surface. Interactions of the lipid headgroups may be responsible for the specific interactions found in tightly bound lipids but seem to have a negligible effect on interactions of generic annular lipids with membrane proteins.

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Comparisons between the EPL and DMPC bilayers. (A) The average distance between the phosphodiester groups in the two leaflets of the bilayer formed by EPLs (31.9 Å) is very similar to that between the phosphodiester groups in the DMPC bilayers (33.6 Å). Phosphorous atoms are shown in orange. Red shading represents the region between the most distantly located phosphorous atoms in each leaflet. (B) Despite the longer acyl chains of EPLs, the average distance between the C2 atoms of the lipids' glycerol backbones in the two leaflets of the bilayer formed by EPLs (27.0 Å) is shorter than that between the C2 atoms in the DMPC bilayers (31.2 Å). The glycerol groups are shown in green. The green shading represents the region between the two most distantly located C2 atoms in each leaflet. (C) Overlay of the lipids seen in the AQP0EPL (red) and AQP0DMPC (blue) structures. (D) Same as in (C) with the lipids coloured according to their B-factors. Colour coding: intense blue, B-factors below 75 Å2; pale blue, B-factors between 75 and 94 Å2; pale red, B-factors between 95 and 114 Å2; intense red, B-factors above 115 Å2.
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f3: Comparisons between the EPL and DMPC bilayers. (A) The average distance between the phosphodiester groups in the two leaflets of the bilayer formed by EPLs (31.9 Å) is very similar to that between the phosphodiester groups in the DMPC bilayers (33.6 Å). Phosphorous atoms are shown in orange. Red shading represents the region between the most distantly located phosphorous atoms in each leaflet. (B) Despite the longer acyl chains of EPLs, the average distance between the C2 atoms of the lipids' glycerol backbones in the two leaflets of the bilayer formed by EPLs (27.0 Å) is shorter than that between the C2 atoms in the DMPC bilayers (31.2 Å). The glycerol groups are shown in green. The green shading represents the region between the two most distantly located C2 atoms in each leaflet. (C) Overlay of the lipids seen in the AQP0EPL (red) and AQP0DMPC (blue) structures. (D) Same as in (C) with the lipids coloured according to their B-factors. Colour coding: intense blue, B-factors below 75 Å2; pale blue, B-factors between 75 and 94 Å2; pale red, B-factors between 95 and 114 Å2; intense red, B-factors above 115 Å2.

Mentions: The EPL and DMPC bilayers surrounding AQP0 are remarkably similar (Figure 2B and C). The two bilayers contain the same number of lipids at comparable positions (Figure 3C) and have almost the same thickness (the average distance between the phosphodiester groups in the two leaflets is 31.9 Å for the EPL bilayer and 33.6 Å for the DMPC bilayer; Figure 3A). As acyl chains of EPLs are on average longer than those of DMPC (16 versus 14 carbon atoms), this finding raises the question how the longer EPL acyl chains are accommodated. Unexpectedly, despite the longer acyl chains of EPLs, the average distance between the C2 atoms of glycerols in the two leaflets of the EPL bilayer, 27.0 Å, is smaller than the corresponding average distance in the DMPC bilayer, 31.2 Å (Figure 3B). Further comparison of the AQP0EPL and AQP0DMPC structures reveals that the DMPC molecules cover less surface area on AQP0 than EPLs (Figures 2B and C). Indeed, the DMPC bilayer leaves areas of the hydrophobic surface of AQP0 uncovered (Figure 2C, e.g. area in between PC3 and PC4 of the extracellular leaflet and PC7 of the cytoplasmic leaflet), suggesting that 14-carbon acyl chains are close to the minimum needed to saturate the hydrophobic belt of AQP0. Furthermore, unlike the lipids in the DMPC bilayer, several of the longer EPL acyl chains interdigitate in the middle of the bilayer, filling gaps between acyl chains in the opposite leaflet (Figure 2B; e.g. one acyl chain of PE7 inserts between the two acyl chains of PE3 and the other acyl chain of PE7 inserts between the two acyl chains of PE4). Other acyl chains bend sharply as they approach the midpoint of the bilayer and then extend parallel to the membrane plane (Figure 2B; e.g. acyl chains of PE4, PE6, and PE7). Such bending may be facilitated by unsaturated bonds present in acyl chains of EPLs, which have previously been proposed to explain the bent conformations seen in lipids associated with cytochrome b–c1 complexes (Palsdottir and Hunte, 2004). Indeed, the positions of the kinks seen in the acyl chains of lipids PE3, PE4, and PE6 occur close to the positions of the double bonds in the most abundant unsaturated acyl chains of EPLs, 16c1:9 and 18c1:11, whereas the kink in the acyl chain of PE7 is located between C6 and C7.


Principles of membrane protein interactions with annular lipids deduced from aquaporin-0 2D crystals.

Hite RK, Li Z, Walz T - EMBO J. (2010)

Comparisons between the EPL and DMPC bilayers. (A) The average distance between the phosphodiester groups in the two leaflets of the bilayer formed by EPLs (31.9 Å) is very similar to that between the phosphodiester groups in the DMPC bilayers (33.6 Å). Phosphorous atoms are shown in orange. Red shading represents the region between the most distantly located phosphorous atoms in each leaflet. (B) Despite the longer acyl chains of EPLs, the average distance between the C2 atoms of the lipids' glycerol backbones in the two leaflets of the bilayer formed by EPLs (27.0 Å) is shorter than that between the C2 atoms in the DMPC bilayers (31.2 Å). The glycerol groups are shown in green. The green shading represents the region between the two most distantly located C2 atoms in each leaflet. (C) Overlay of the lipids seen in the AQP0EPL (red) and AQP0DMPC (blue) structures. (D) Same as in (C) with the lipids coloured according to their B-factors. Colour coding: intense blue, B-factors below 75 Å2; pale blue, B-factors between 75 and 94 Å2; pale red, B-factors between 95 and 114 Å2; intense red, B-factors above 115 Å2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2876970&req=5

f3: Comparisons between the EPL and DMPC bilayers. (A) The average distance between the phosphodiester groups in the two leaflets of the bilayer formed by EPLs (31.9 Å) is very similar to that between the phosphodiester groups in the DMPC bilayers (33.6 Å). Phosphorous atoms are shown in orange. Red shading represents the region between the most distantly located phosphorous atoms in each leaflet. (B) Despite the longer acyl chains of EPLs, the average distance between the C2 atoms of the lipids' glycerol backbones in the two leaflets of the bilayer formed by EPLs (27.0 Å) is shorter than that between the C2 atoms in the DMPC bilayers (31.2 Å). The glycerol groups are shown in green. The green shading represents the region between the two most distantly located C2 atoms in each leaflet. (C) Overlay of the lipids seen in the AQP0EPL (red) and AQP0DMPC (blue) structures. (D) Same as in (C) with the lipids coloured according to their B-factors. Colour coding: intense blue, B-factors below 75 Å2; pale blue, B-factors between 75 and 94 Å2; pale red, B-factors between 95 and 114 Å2; intense red, B-factors above 115 Å2.
Mentions: The EPL and DMPC bilayers surrounding AQP0 are remarkably similar (Figure 2B and C). The two bilayers contain the same number of lipids at comparable positions (Figure 3C) and have almost the same thickness (the average distance between the phosphodiester groups in the two leaflets is 31.9 Å for the EPL bilayer and 33.6 Å for the DMPC bilayer; Figure 3A). As acyl chains of EPLs are on average longer than those of DMPC (16 versus 14 carbon atoms), this finding raises the question how the longer EPL acyl chains are accommodated. Unexpectedly, despite the longer acyl chains of EPLs, the average distance between the C2 atoms of glycerols in the two leaflets of the EPL bilayer, 27.0 Å, is smaller than the corresponding average distance in the DMPC bilayer, 31.2 Å (Figure 3B). Further comparison of the AQP0EPL and AQP0DMPC structures reveals that the DMPC molecules cover less surface area on AQP0 than EPLs (Figures 2B and C). Indeed, the DMPC bilayer leaves areas of the hydrophobic surface of AQP0 uncovered (Figure 2C, e.g. area in between PC3 and PC4 of the extracellular leaflet and PC7 of the cytoplasmic leaflet), suggesting that 14-carbon acyl chains are close to the minimum needed to saturate the hydrophobic belt of AQP0. Furthermore, unlike the lipids in the DMPC bilayer, several of the longer EPL acyl chains interdigitate in the middle of the bilayer, filling gaps between acyl chains in the opposite leaflet (Figure 2B; e.g. one acyl chain of PE7 inserts between the two acyl chains of PE3 and the other acyl chain of PE7 inserts between the two acyl chains of PE4). Other acyl chains bend sharply as they approach the midpoint of the bilayer and then extend parallel to the membrane plane (Figure 2B; e.g. acyl chains of PE4, PE6, and PE7). Such bending may be facilitated by unsaturated bonds present in acyl chains of EPLs, which have previously been proposed to explain the bent conformations seen in lipids associated with cytochrome b–c1 complexes (Palsdottir and Hunte, 2004). Indeed, the positions of the kinks seen in the acyl chains of lipids PE3, PE4, and PE6 occur close to the positions of the double bonds in the most abundant unsaturated acyl chains of EPLs, 16c1:9 and 18c1:11, whereas the kink in the acyl chain of PE7 is located between C6 and C7.

Bottom Line: Comparison of the two structures shows that AQP0 does not adapt to the different length of the acyl chains in EPLs and that the distance between the phosphodiester groups in the two leaflets of the DMPC and EPL bilayers is almost identical.The interactions of annular lipids with membrane proteins seem to be driven by the propensity of the acyl chains to fill gaps in the protein surface.Interactions of the lipid headgroups may be responsible for the specific interactions found in tightly bound lipids but seem to have a negligible effect on interactions of generic annular lipids with membrane proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT
We have previously described the interactions of aquaporin-0 (AQP0) with dimyristoyl phosphatidylcholine (DMPC) lipids. We have now determined the 2.5 A structure of AQP0 in two-dimensional (2D) crystals formed with Escherichia coli polar lipids (EPLs), which differ from DMPC both in headgroups and acyl chains. Comparison of the two structures shows that AQP0 does not adapt to the different length of the acyl chains in EPLs and that the distance between the phosphodiester groups in the two leaflets of the DMPC and EPL bilayers is almost identical. The EPL headgroups interact differently with AQP0 than do those of DMPC, but the acyl chains in the EPL and DMPC bilayers occupy similar positions. The interactions of annular lipids with membrane proteins seem to be driven by the propensity of the acyl chains to fill gaps in the protein surface. Interactions of the lipid headgroups may be responsible for the specific interactions found in tightly bound lipids but seem to have a negligible effect on interactions of generic annular lipids with membrane proteins.

Show MeSH
Related in: MedlinePlus