Electrostatic Contributions to Indole−Lipid Interactions

Gaede, Holly C.; Yau, Wai‐Ming; Gawrisch, Klaus

doi:10.1021/jp0511000

Cited by 89 publications

(114 citation statements)

References 38 publications

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“…Aromatics have both polar and hydrophobic characters and are known to favor the lipid-water interface location (33). Flanking aromatics confer resistance against displacement to experimental peptides embedded in bilayers (34,35). A survey of residue distribution shows interfacial preference for tryptophan, tyrosine, and histidine, although not for phenylalanine (36).…”

Section: Homologous Mutations In the Yeast Trpy1 And The Fly Trpc1 Havementioning

confidence: 99%

Yeast gain-of-function mutations reveal structure–function relationships conserved among different subfamilies of transient receptor potential channels

Su¹,

Zhou²,

Haynes³

et al. 2007

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

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Section: Homologous Mutations In the Yeast Trpy1 And The Fly Trpc1 Havementioning

confidence: 99%

Yeast gain-of-function mutations reveal structure–function relationships conserved among different subfamilies of transient receptor potential channels

Su¹,

Zhou²,

Haynes³

et al. 2007

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

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“…A trace of approximately 30 s was analyzed for events greater than 1 ms (>200 events) at each holding potential using Clampfit 10.0 (pClamp 10.0). The mean current amplitudes of each seal were averaged, plotted and fitted to a linear equation using GraphPad Prims v. 4. The mean open time was determined by selecting open events using the half-amplitude criterion and plotting it in a histogram of the logarithm of open time using Clampfit 10.0.…”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3] Tryptophan and tyrosine tend to localize at the water-hydrocarbon core interface (WHc interface, also known as polar "head groups") near the carbonyl region of the membrane as has been demonstrated by molecular simulations of integral proteins, high-resolution structural studies of integral proteins, and NMR studies with tryptophan analogs. [4][5][6][7][8] Phenylalanine also tends to be localized at the WHc interface, but can also be accommodated within the hydrocarbon core. 1 Studies on small peptides, tryptophan-analog molecules and simulations studies, suggest that the tendency to be located at the WHc interface arises from a combination of intermolecular interactions and entropic effects associated with the rigid aromatic ring.…”

Section: Introductionmentioning

confidence: 99%

“…1 Studies on small peptides, tryptophan-analog molecules and simulations studies, suggest that the tendency to be located at the WHc interface arises from a combination of intermolecular interactions and entropic effects associated with the rigid aromatic ring. 4,[9][10][11] It has been proposed that these are mainly van der Waals and cation-π interactions. Dipole interactions and hydrogen bonding contribute to localization but are not essential.…”

Section: Introductionmentioning

confidence: 99%

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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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“…12,13 NMR studies on indole derivatives embedded in lipid bilayers have 40 demonstrated that the dipole moment of the indole group, cation-π interactions and the ability of the indole group to participate in hydrogen bonding interactions with lipids all contribute to localisation in the interfacial region. 11,[14][15][16] More recently however, steric effects and dipole-dipole 45 contributions have been suggested to be more important than hydrogen bonding or cation-π interactions for determining the membrane partitioning and alignment of these and related indole derivatives. 10 Molecular dynamics simulations of mixed indole-lipid and tryptophan-lipid systems indicate a 50 preference for indole to localise at specific locations in relation to membranes, including the middle of the bilayer, proximal to the choline headgroup and in the region of the lipid carbonyl groups, with the latter being the preferred site.…”

Section: Introductionmentioning

confidence: 99%

Free-energy relationships for the interactions of tryptophan with phosphocholines

2009

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Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. In membrane proteins and peptides, tryptophan exhibits a marked tendency to occur in locations that correspond to the interfacial region of the lipid bilayer. The relative contributions of electrostatic, dipolar, hydrophobic and conformational effects on the interactions of tryptophan with lipids have been the subject of much speculation. In order to elucidate the fundamental 10 properties of tryptophan-phosphocholine interactions in the absence of competing factors such as protein conformation and membrane perturbation, we have determined the binding characteristics of a homologous series of tryptophan analogues to 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in deuterochloroform using NMR titrimetric approaches. The data are analysed using a binding model that includes lipid aggregation and the explicit association of water with the lipid. 15For a series of substituents (OMe, Me, H, F, Cl, Br, I, NO 2 ) at the 5-position of the indole ring, the trends in the free energy of association for the formation of 1:1 and 1:2 lipid:tryptophan adducts both follow an inverted-U relationship as a function of the corresponding para-Hammett parameter, with tryptophan (R = H) exhibiting the weakest binding. These trends are shown to be consistent with participation of the indole side chain in both hydrogen bonds and cation-π interactions. 20Molecular dynamics simulations of tryptophan and DMPC in an explicit chloroform solvent model demonstrate that for the formation of lipid-tryptophan adducts, binding is driven predominantly by carbonyl-cation and cation-π interactions with the choline ammonium group, alongside hydrogen bonding interactions with the lipid phosphate. Some of these interactions operate co-operatively, which may account for the observed trends in free energy.

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Electrostatic Contributions to Indole−Lipid Interactions

Cited by 89 publications

References 38 publications

Yeast gain-of-function mutations reveal structure–function relationships conserved among different subfamilies of transient receptor potential channels

Yeast gain-of-function mutations reveal structure–function relationships conserved among different subfamilies of transient receptor potential channels

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

Free-energy relationships for the interactions of tryptophan with phosphocholines

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