The Conduction of Protons in Different Stereoisomers of Dioxolane-Linked Gramicidin A Channels

Abstract

Two different stereoisomers of the dioxolane-linked gramicidin A (gA) channels were individually synthesized (the SS and RR dimers;. Science. 244:813-817). The structural differences between these dimers arise from different chiralities within the dioxolane linker. The SS dimer mimics the helicity and the inter- and intramolecular hydrogen bonding of the monomer-monomer association of gA's. In contrast, there is a significant disruption of the helicity and hydrogen bonding pattern of the ion channel in the RR dimer. Single ion channels formed by the SS and RR dimers in planar lipid bilayers have different proton transport properties. The lipid environment in which the different dimers are reconstituted also has significant effects on single-channel proton conductance (g(H)). g(H) in the SS dimer is about 2-4 times as large as in the RR. In phospholipid bilayers with 1 M [H(+)](bulk), the current-voltage (I-V) relationship of the SS dimer is sublinear. Under identical experimental conditions, the I-V plot of the RR dimer is supralinear (S-shaped). In glycerylmonooleate bilayers with 1 M [H(+)](bulk), both the SS and RR dimers have a supralinear I-V plot. Consistent with results previously published (. Biophys. J. 73:2489-2502), the SS dimer is stable in lipid bilayers and has fast closures. In contrast, the open state of the RR channel has closed states that can last a few seconds, and the channel eventually inactivates into a closed state in either phospholipid or glycerylmonooleate bilayers. It is concluded that the water dynamics inside the pore as related to proton wire transfer is significantly different in the RR and SS dimers. Different physical mechanisms that could account for this hypothesis are discussed. The gating of the synthetic gA dimers seems to depend on the conformation of the dioxolane link between gA's. The experimental results provide an important framework for a detailed investigation at the atomic level of proton conduction in different and relatively simple ion channel structures.

An insight into the disorder properties of the α-cyclodextrin polyiodide inclusion complex with Sr2+ ion: dielectric, DSC and FT-Raman spectroscopy studies

“…These findings explicitly indicate that the aforementioned inclusion complexes are excellent models for the elucidation of principal forces, dynamic properties and charge transport mechanisms in the water clusters of biological systems (10)(11)(12)(13)(14), in the building blocks of many polyiodide materials (15) and in the cyclodextrin complex formation processes (16,17). Despite the fact that the individual nature of each counterion appears 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 The temperature variation was controlled with a Ventacon Winchester instrument equipped with a CALCOMMS 3300 autotune controller.…”

Numerical framework models of single proton conduction through Gramicidin

“…This result suggests that an analysis of water permeation through gramicidin which refers only to this one degree of freedom would be appropriate. However, the number of essential coordinates required to describe the permeation process is likely to increase as the channel environment is made more complex (13,15) or as the pore radius increases (32). The development of numerical methods for constructing framework models would then be required to apply this approach to the description of these more complex molecular motions.…”

“…If the movements of the center of charge and of the defects are substantially independent, two or more degrees of freedom may be required to describe their interaction. A second example is provided by the RR dioxolane linked analogs of gramicidin (12)(13)(14). Molecular modeling suggests that the backbone carbonyls closest to the dimer interface can flip between orientations of almost equal energy, one projecting at an angle of 20-30° into the pore and the other projecting at an angle of 20-30° away from the pore (15).…”

Proton Transfer in Gramicidin Water Wires in Phospholipid Bilayers: Attenuation by Phosphoethanolamine

“…The permeation of protons in gA channels does not seem to occur via hydrodynamic diffusion of protonated waters. Instead, an H 1 transfer Grotthuss-type mechanism may occur in various gA channels (5,6,(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

“…Moreover, proton transfer can be measured in a single channel molecule. Recent work from our laboratory (10)(11)(12)16,(22)(23)(24) have used the SS and RR diastereoisomers of dioxolane-linked gA channels (16,25) to measure H 1 transfer in water wires, and to correlate those experimental measurements with possible molecular mechanisms (16,26). It was suggested that the chiral centers of the dioxolane linker underlie the profound quantitative and qualitative differences in the rate of H 1 transfer in distinct gA channels.…”