Water‐mediated conformational transitions in nicotinic receptor M2 helix bundles: a molecular dynamics study

doi:10.1016/0014-5793(95)01376-8

Cited by 25 publications

(6 citation statements)

References 33 publications

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“…Knowledge of dynamics of hydration at the molecular level is of considerable importance in understanding the cellular structure and function since water plays a crucial role in the formation and maintenance of organized molecular assemblies such as proteins and membranes in a cellular environment. ,,,,,, In addition, water plays a crucial role in mediating lipid−protein interactions thereby controlling the functionality of membrane proteins. ,,, For example, it was shown earlier using neutron diffraction of small peptides in membrane bilayers that there was a direct association of water with the peptides, possibly with a tryptophan residue . It was suggested that such an effect, if enhanced by larger peptides, would be important for the insertion of helices into bilayers and for helix−helix interactions involving hydrogen bonding.…”

Section: Discussionmentioning

confidence: 99%

“…Hydration plays a key role in cell structure and function and is crucial for lipid−protein interactions in membranes . Water plays a crucial role in determining the structure and dynamics, and in turn the function of proteins. , It is estimated that a threshold level of hydration (less than 0.4 g of water per gram of protein) is required to fully activate the dynamics and function of globular proteins. − In addition, it has become increasingly evident that water molecules mediate lipid−protein interactions ,, and hence the function of membrane proteins. , Any alteration in the degree of hydration, particularly at the protein−lipid interface in cell membranes, could potentially lead to modifications of proteinstructure that could in turn modify its function. , Further, it has been established that there is a “bound” hydration shell surrounding the headgroup of membrane phospholipids which plays an important role in membrane stability . In this paper, we have examined the effect of hydration on melittin−membrane interactions by using reverse micelles formed by AOT (sodium bis(2-ethylhexyl) sulfosuccinate) in heptane as a membrane−mimetic system.…”

Section: Introductionmentioning

confidence: 99%

“…Utilizing this approach, it becomes possible to probe the mobility parameters of the environment itself (which is represented by the relaxing solvent molecules) using the fluorophore merely as a reporter group. This makes the use of REES in particular and the wavelength-selective fluorescence approach in general very useful since hydration plays a crucial modulatory role in a large number of important cellular events such as protein folding, lipid−protein interactions, and ion transport. ,,, An in-depth discussion of the photophysical framework for REES and wavelength-selective fluorescence approach is provided in recent reviews. , …”

Section: Introductionmentioning

confidence: 99%

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Organization and Dynamics of Melittin in Environments of Graded Hydration: A Fluorescence Approach

Raghuraman

Chattopadhyay

2003

Langmuir

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Melittin is a cationic hemolytic peptide composed of 26 amino acid residues. It is intrinsically fluorescent because of the presence of a single tryptophan residue which has been shown to be crucial for its hemolytic activity. We have previously shown that the sole tryptophan of melittin is located in a motionally restricted region in the membrane and the tryptophan environment is modulated in the presence of negatively charged phospholipids. Reverse micelles represent a type of organized molecular assembly which offer the unique advantage of monitoring dynamics of embedded molecules with varying degrees of hydration. We have employed reverse micelles as a membrane-mimetic system to monitor the effect of hydration on the organization and dynamics of melittin. Our results show that fluorescence parameters such as intensity, emission maximum, and polarization of melittin incorporated in reverse micelles of AOT in heptane are dependent on [water]/[surfactant] molar ratio (wo) of the reverse micelle. Time-resolved fluorescence measurements of melittin in AOT reverse micelles show a gradual reduction in mean lifetime with increasing w o. More importantly, melittin in reverse micellar environment showed red edge excitation shift (REES) implying that localization of the peptide in reverse micelles results in considerable restriction to the reorientational motion of the solvent dipoles around the excited-state fluorophore. Interestingly, the extent of REES decreased with increasing w o. Fluorescence polarization of melittin in reverse micellar environments was wavelength-dependent. In addition, increasing hydration causes significant increase in helicity of melittin bound to reverse micelles. Taken together, our results provide information about the dynamics of melittin in environments of graded hydration and are relevant to dynamics of membrane-bound peptides under conditions of differential hydration which are more difficult to analyze experimentally.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Organization and Dynamics of Melittin in Environments of Graded Hydration: A Fluorescence Approach

Raghuraman

Chattopadhyay

2003

Langmuir

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“…Further, since the ubiquitous solvent for biological systems is water, the information obtained in such cases will come from the otherwise “optically silent” water molecules. This makes REES and related techniques extremely useful since hydration plays a crucial modulatory role in a large number of important cellular events, including lipid−protein interactions and ion transport. − We have previously shown that REES and related techniques (wavelength-selective fluorescence approach) serve as a powerful tool to monitor organization and dynamics of probes and peptides bound to membranes or micelles. ,,− …”

Section: Introductionmentioning

confidence: 99%

Depth-Dependent Solvent Relaxation in Membranes: Wavelength-Selective Fluorescence as a Membrane Dipstick

Chattopadhyay

Mukherjee

1999

Langmuir

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Membrane penetration depth represents an important parameter which can be used to define the conformation and topology of membrane proteins and probes. We have previously characterized a set of fluorescence spectroscopic approaches, collectively referred to as wavelength-selective fluorescence, as a powerful tool to monitor microenvironments in the vicinity of reporter fluorophores embedded in the membrane. Since several membrane parameters that characterize local environments such as polarity, fluidity, segmental motion, degree of water penetration, and the ability to form hydrogen bonds are known to vary as a function of depth of penetration into the membrane, we propose that wavelength-selective fluorescence could provide a novel approach to investigate the depth of membrane penetration of a reporter fluorophore. We test this hypothesis by demonstrating that chemically identical fluorophores, varying solely in terms of their localization at different depths in the membrane, experience very different local environments, as judged by wavelength-selective fluorescence parameters. We used two anthryoloxy stearic acid derivatives where the anthroyloxy group has previously been found to be either shallow (2-AS) or deep (12-AS). Our results show that the anthroyloxy moiety of 2- and 12-AS experiences different local membrane microenvironments, as reflected by varying extents of red-edge excitation shift (REES) as well as varying degrees of wavelength dependence of fluorescence polarization and lifetime and rotational correlation times. We attribute these results to differential rates of solvent reorientation in the immediate vicinity of the anthroyloxy group as a function of its membrane penetration depth. We thus provide evidence, for the first time, of depth-dependent solvent relaxation which can be used as a membrane dipstick.

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“…Further, since the ubiquitous solvent for biological systems is water, the information obtained in such cases will come from the otherwise “optically silent” water molecules. This makes REES and related techniques extremely useful since hydration plays a crucial modulatory role in a large number of important cellular events, including lipid−protein interactions and ion transport. − We have previously shown that REES and related techniques (collectively termed as wavelength-selective fluorescence approach) can be used to study motional restriction experienced by membrane-bound molecules and serve as a powerful tool to monitor organization and dynamics of probes and peptides bound to membranes or micelles. ,− …”

Section: Introductionmentioning

confidence: 99%

Red Edge Excitation Shift of a Deeply Embedded Membrane Probe: Implications in Water Penetration in the Bilayer

1999

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The biological membrane is a highly organized anisotropic molecular assembly. While the center of the bilayer is nearly isotropic, the upper portion, only a few angstroms away toward the membrane surface, is highly ordered. How this organization correlates with the degree of water penetration into the bilayer interior is not clear. In general, it is believed that there is not much water in the deeper hydrocarbon regions of the bilayer. In this study, we have utilized the phenomenon of wavelength-selective fluorescence to address this question. We show here that when the same fluorescent group (i.e., 7-nitrobenz-2-oxa-1,3-diazol-4-yl or NBD) is localized at different depths within the bilayer (viz., near the membrane interface in case of the headgroup-labeled NBD-phosphatidylethanolamine (NBD-PE) and near the center of the bilayer in NBD-cholesterol), the degrees to which their fluorescence properties exhibit solvent-induced effects are markedly different. For example, the headgroup-labeled NBD-PE exhibits a much stronger red edge excitation shift (REES) relative to that of NBD-cholesterol. This indicates lesser restriction to mobility in this region as compared to the polar/hydrocarbon interface. In the gel phase, however, REES of NBD-PE did not show any significant change while NBDcholesterol exhibited no REES. In addition, NBD-cholesterol exhibits a stronger dependence of fluorescence polarization on excitation wavelength in fluid membranes. We attribute these results to the more compact arrangement of the lipid acyl chains in the gel phase which results in lesser water penetration. Since the hydrophobic core of the lipid bilayer is made up of methyl and methylene groups, the only solvent dipoles capable of any interaction with the dipole of the fluorophore giving rise to the REES effect in the fluid phase have to be water molecules that have penetrated deep into the bilayer close to the NBD moiety of NBDcholesterol. Our results indicate that at least in the fluid phase of the membrane, penetration of water in the deep hydrocarbon region of the bilayer does indeed occur.

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Water‐mediated conformational transitions in nicotinic receptor M2 helix bundles: a molecular dynamics study

Cited by 25 publications

References 33 publications

Organization and Dynamics of Melittin in Environments of Graded Hydration: A Fluorescence Approach

Organization and Dynamics of Melittin in Environments of Graded Hydration: A Fluorescence Approach

Depth-Dependent Solvent Relaxation in Membranes: Wavelength-Selective Fluorescence as a Membrane Dipstick

Red Edge Excitation Shift of a Deeply Embedded Membrane Probe: Implications in Water Penetration in the Bilayer

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