Interactions of Phospholipids with the Potassium Channel KcsA

Williamson, Ian M.; Alvis, Simon J.; East, J. Malcolm; Lee, Anthony G.

doi:10.1016/s0006-3495(02)73964-7

Cited by 99 publications

(132 citation statements)

References 50 publications

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“…This fatty acid/␣-helix interaction is highly dependent on the chain length. Binding occurs with a minimum acyl chain length of 10 carbons and becomes optimal at a tail length of 22 carbons (30). This matches very closely with our data showing an effect on K ATP channel activity with acyl chains of Ն14 carbons (Fig.…”

Section: Discussionsupporting

confidence: 91%

Saturated and cis/trans Unsaturated Acyl CoA Esters Differentially Regulate Wild-Type and Polymorphic β-Cell ATP-Sensitive K+ Channels

Riedel

Light

2005

Diabetes

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Section: Discussionsupporting

confidence: 91%

Saturated and cis/trans Unsaturated Acyl CoA Esters Differentially Regulate Wild-Type and Polymorphic β-Cell ATP-Sensitive K+ Channels

Riedel

Light

2005

Diabetes

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“…This conclusion is further substantiated by the results of the mixtures of the unsaturated PC species. Also in these systems no molecular sorting takes place under Literature data so far have shown molecular sorting of lipids to occur to various extents for a number of membrane proteins (5)(6)(7)(8). Then why do we not observe it in our systems?…”

Section: Discussionmentioning

confidence: 69%

“…Previously, this has been probed mainly by fluorescence and ESR 1 methods using labeled lipids (5)(6)(7)(8)(9)(10)(11). In this study, we explore a more direct method to investigate the immediate surroundings of membrane proteins.…”

mentioning

confidence: 99%

Photo-Crosslinking Analysis of Preferential Interactions between a Transmembrane Peptide and Matching Lipids

et al. 2004

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In this study, a novel method is presented by which the molecular environment of a transmembrane peptide can be investigated directly. This was achieved by incorporating a photoactivatable crosslinking probe in the hydrophobic segment of a model transmembrane peptide. When this peptide was incorporated into lipid bilayers and irradiated with UV light, a covalent bond was formed between the crosslinking probe and a lipid. This crosslinking reaction could be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the resulting product could be characterized by mass spectrometry. By use of phospholipases, it was demonstrated that the peptide crosslinks to both acyl chains of the lipids. The peptide showed a clear preference to partition into fluid lipids and was excluded from lipids in the gel phase. However, when the peptide was incorporated into bilayers containing two lipid species with different acyl chain lengths, molecular sorting of the lipids around the peptide based on hydrophobic matching was not observed. It is proposed that the size of the transmembrane part plays an important role in the dynamic interactions of membrane proteins with the surrounding lipids and hence in determining whether molecular sorting can occur.Proteins in biological membranes reside in a complex environment in which they are surrounded by many different lipid species. Transmembrane proteins can have different affinities for different lipids, and as a result particular lipids or members of particular lipid classes may become enriched around a certain protein. Such differences in affinity may be due to specific interactions with the lipid headgroups or the lipid acyl chains. An example of the latter would be the enrichment of matching lipids around a protein, which could be a mechanism by which mismatches between hydrophobic transmembrane segments and the hydrophobic thickness of the lipid bilayer can be relieved. Such a mechanism of molecular sorting by transmembrane proteins has been predicted from theoretical calculations (1, 2; reviewed in refs 3 and 4) and has indeed been shown to occur for several transmembrane proteins (5-8).To gain insight into the role of protein-lipid interactions in the sorting of lipids around specific proteins, tools must be available to determine the lipid environment of membrane proteins. Previously, this has been probed mainly by fluorescence and ESR 1 methods using labeled lipids (5-11). In this study, we explore a more direct method to investigate the immediate surroundings of membrane proteins. For this purpose we make use of a synthetic model peptide, which contains a photoactivatable probe that is able to form covalent bonds with the surrounding lipids upon UV irradiation. The crosslinking reaction can be visualized by SDS-PAGE analysis and the identity of the lipid that is crosslinked to the peptide can subsequently be characterized by mass spectrometry.

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“…42 (3) In KcsA potassium channel, tryptophans located at the WHc interface experienced a slightly change of environment when the hydrophobic length of the membrane was modified. 43 The environment of tryptophans was the same for the conducting and nonconducting states suggesting that aromatics residues remain at a specific membrane location. (4) The effective hydrophobic length of the transmembrane domains was potentially delimited by flanking aromatic residues.…”

Section: Discussionmentioning

confidence: 98%

Aromaticity at the Water-Hydrocarbon Core Interface of the Membrane: Consequences on the Nicotinic Acetylcholine Receptor

et al. 2008

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Almost all lipid-exposed transmembrane domains of integral proteins contain aromatic residues flanking the hydrophobic segment of the domains. These residues generally reside close to the carbonyl region of the membrane, and several structural and functional roles have been associated to these residues. Although the roles and physicochemical reasons for aromatic preference have been extensively studied using model systems, few studies have been done in a native membrane system. To gain insight about the mechanistic implication for this aromatic preference, we selected position αF426 of the muscle-type nicotinic acetylcholine receptor (nAChR). αF426 is a lipid-exposed residue at the extracellular segment of the αM4 transmembrane domain and is highly conserved among different nAChR subunits and species. We used site-directed mutagenesis, α-Bungarotoxin-binding assay, and two-electrodes voltage clamp in Xenopus laevis oocytes to characterize mutations at position αF426, which impart different physicochemical properties like volume, polarity, hydrogen bonds, aromaticity and net electrical charge. All mutations except the aromatic residues resulted in a significant reduction of the nAChR cell-surface levels and the macroscopic currents to acetylcholine. These results suggest that position αF426 contributes to structural stability and open-close transitions of the nAChR. Finally, the present study also provides information about how intermolecular interactions at position α426 modulate open-close transitions of the nAChR.

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Interactions of Phospholipids with the Potassium Channel KcsA

Cited by 99 publications

References 50 publications

Saturated and cis/trans Unsaturated Acyl CoA Esters Differentially Regulate Wild-Type and Polymorphic β-Cell ATP-Sensitive K+ Channels

Saturated and cis/trans Unsaturated Acyl CoA Esters Differentially Regulate Wild-Type and Polymorphic β-Cell ATP-Sensitive K+ Channels

Photo-Crosslinking Analysis of Preferential Interactions between a Transmembrane Peptide and Matching Lipids

Aromaticity at the Water-Hydrocarbon Core Interface of the Membrane: Consequences on the Nicotinic Acetylcholine Receptor

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