Effects of Bilayer Thickness on the Activity of Diacylglycerol Kinase of <i>Escherichia coli</i>

Pilot, J D; East, J. Malcolm; Lee, A G

doi:10.1021/bi0103258

Cited by 64 publications

(65 citation statements)

References 38 publications

(63 reference statements)

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“…Hydrophobic matching modulates the activity of several purified integral membrane proteins, such as Na,K-ATPase (3,4), cytochrome c oxidase (5), Ca-ATPase (6, 7), melibiose permease (8), and diacylglycerol kinase (9), when they are reconstituted into pure phospholipid bilayers. The segregation and partition of proteins and lipids into distinctively functional areas in the membrane might also be influenced by hydrophobic matching (10).…”

mentioning

confidence: 99%

Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol

Mitra

Ubarretxena-Belandia

Taguchi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

403

307

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A biological membrane is conceptualized as a system in which membrane proteins are naturally matched to the equilibrium thickness of the lipid bilayer. Cholesterol, in addition to lipid composition, has been suggested to be a major regulator of bilayer thickness in vivo because measurements in vitro have shown that cholesterol can increase the thickness of simple phospholipid͞cholesterol bilayers. Using solution x-ray scattering, we have directly measured the average bilayer thickness of exocytic pathway membranes, which contain increasing amounts of cholesterol. The bilayer thickness of membranes of the endoplasmic reticulum, the Golgi, and the basolateral and apical plasma membranes, purified from rat hepatocytes, were determined to be 37.5 ؎ 0.4 Å, 39.5 ؎ 0.4 Å, 35.6 ؎ 0.6 Å, and 42.5 ؎ 0.3 Å, respectively. After cholesterol depletion using cyclodextrins, Golgi and apical plasma membranes retained their respective bilayer thicknesses whereas the bilayer thickness of the endoplasmic reticulum and the basolateral plasma membrane decreased by 1.0 Å. Because cholesterol was shown to have a marginal effect on the thickness of these membranes, we measured whether membrane proteins could modulate thickness. Protein-depleted membranes demonstrated changes in thickness of up to 5 Å, suggesting that (i) membrane proteins rather than cholesterol modulate the average bilayer thickness of eukaryotic cell membranes, and (ii) proteins and lipids are not naturally hydrophobically matched in some biological membranes. A marked effect of membrane proteins on the thickness of Escherichia coli cytoplasmic membranes, which do not contain cholesterol, was also observed, emphasizing the generality of our findings.

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mentioning

confidence: 99%

Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol

Mitra

Ubarretxena-Belandia

Taguchi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

403

307

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“…The lipid composition of the membrane can have significant effects on, and even regulate, membrane protein function. In a number of cases, protein function is proposed to be influenced by the bulk physico-chemical properties of the membrane, which in turn are strictly determined by the exact lipid composition of the bilayer (2)(3)(4). Such properties include hydrophobic thickness (4), phase transition (5), curvature (6), and lateral pressure (3).…”

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confidence: 99%

Lipid Composition Regulates the Orientation of Transmembrane Helices in HorA, an ABC Multidrug Transporter

Gustot

Smriti

Ruysschaert

et al. 2010

Journal of Biological Chemistry

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ATP-binding cassette (ABC) transporters constitute a large class of molecular pumps whose central role in chemotherapy resistance has highlighted their clinical relevance. We investigated whether the lipid composition of the membrane affects the function and structure of HorA, a bacterial ABC multidrug transporter. When the transporter was reconstituted in a bilayer where phosphatidylethanolamine (PE), the main lipid of the bacterial membrane, was replaced with phosphatidylcholine (PC), ATP hydrolysis and substrate transport became uncoupled. Although ATPase activity was maintained, HorA lost its ability to extrude the prototypical substrate Hoechst33342. Attenuated Total Reflection-Fourier Transform Infrared spectroscopy (ATR-FTIR) revealed that, although the secondary structure of the protein was unaffected, the orientation of the transmembrane helices (TM) was modified by the change in lipid composition. The orientation of the backbone carbonyls indicated that the helices opened wider in PE versus PC-containing liposomes, with 10 degrees difference. This was supported by hydrogen/deuterium exchange studies showing increased protection of the backbone from the solvent in PC-containing liposomes. Electron Paramagnetic Resonance was used to further probe the structural change. In the PC-containing liposomes we observed increased mobility of the spin label in TM4, along with increased exposure to molecular oxygen, used as a hydrophobic quencher. This indicates that the lipid change induced modification of the orientation of TM4, exposing Cys-180 to the lipid phase. The lipid composition of the bilayer thus modulates the structure of HorA, and in turn its ability to extrude its substrates.Over the last thirty years, our vision of the biological membrane has evolved from the fluid mosaic model (1) to that of a remarkably complex system where a myriad of molecules are tightly organized along the membrane plane to properly interact and achieve numerous biological functions.Precise interplay between lipids and proteins must occur to achieve biological function, and membrane proteins have evolved specific sequence motifs to adapt to their environment. Studies have begun to evidence how proteins and lipids interact. It emerges notably that membrane proteins are surrounded by a shell of slow-moving lipids (annular lipids) distinguishable from the bulk phase. Other lipids (non-annular lipids) can achieve tight and specific interactions with a protein and act as cofactors essential to protein function (2, 3). The lipid composition of the membrane can have significant effects on, and even regulate, membrane protein function. In a number of cases, protein function is proposed to be influenced by the bulk physico-chemical properties of the membrane, which in turn are strictly determined by the exact lipid composition of the bilayer (2-4). Such properties include hydrophobic thickness (4), phase transition (5), curvature (6), and lateral pressure (3). It has also been proposed that a specific lipid might act as a molecular cha...

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“…Specific examples of enzyme activity influenced by bilayer thickness are the Ca 2ϩ Mg 2ϩ ATPase (10,11), diacylglycerol kinase (12), rhodopsin (13), the human erythrocyte hexose transporter (14), and the Na ϩ K ϩ ATPase (15). Several lines of evidence have established that this parameter of the membrane bilayer also plays an important role in regulating the sorting of proteins between the Golgi complex and the plasma membrane.…”

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confidence: 99%

Regulation of the Gating of BKCa Channel by Lipid Bilayer Thickness

Yuan

O’Connell

Jacob³

et al. 2007

Journal of Biological Chemistry

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Effects of Bilayer Thickness on the Activity of Diacylglycerol Kinase of Escherichia coli

Cited by 64 publications

References 38 publications

Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol

Modulation of the bilayer thickness of exocytic pathway membranes by membrane proteins rather than cholesterol

Lipid Composition Regulates the Orientation of Transmembrane Helices in HorA, an ABC Multidrug Transporter

Regulation of the Gating of BKCa Channel by Lipid Bilayer Thickness

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