Lipid conformational states

The order parameters are mostly used to judge the correspondence of the obtained results to the experiment. Three different kinds of order parameters are used in the literature to characterize the conformational state of the lipid alkyl chains. The first is SCD, which can be obtained directly from the quadrupolar splitting of selectively deuterated phospholipids by NMR. SCD is related to the observed quadrupolar splitting by Eq. 6.5 ... 

Conformational states and spatial organizations of lipids. Small circles indicate the polar head group region of the molecules, whereas hydrophobic chains are represented as single lines. 

Figure 3.21. Monte Carlo surface pressure Isotherms for lipid-like molecules having 10 different conformational states available. 10.000 chains anchoring groups not specified. The filled circles are computed drawn lines are guides for the eye. Model parameters mimic dlpalmltoyl phosphatidyl choline (DPPC) monolayers. (Redrawn from Mouritsen et al. (1989).)...

Information on the conformational state of the hydrocarbon chains and their orientation has been obtained from external infrared reflection absorption spectroscopy (IRRAS). The first systematic IRRAS studies on phospholipid Langmuir monolayers were reported by Dluhy et al ) (see, for instance fig. 3.62). For DPPC monolayers in the LE phase the positions of the conformation-sensitive symmetric and anti-symmetric C-H stretching bands in the IRRAS spectra were found to be at the same positions as for bilayer systems of DPPC above the Kralft temperature. In the LC phase the frequencies of these bands indicate that the hydrocarbon chains of the lipid molecules are in the all-trans ) conformation (i.e. zig-zag) and analysis of polarized IRRAS spectra show that their average tilt is ca 35° relative to the monolayer normal. This is in reasonable agreement with the tilt angle of 30° obtciined from X-ray diffraction on DPPC monolayers (30°). 

The crystal structures of lipases described to date are static descriptions of conformational states, possibly stabilized in some cases by crystal packing interactions. What is lacking is the dynamic component What initiates the conformational transition Is there a true lipid-recognition site that triggers the change, and does a simple two-state model come sufficiently close to the actual phenomenon Or, does the interface simply stabilize one of the conformations existing in solution in an equilibrium And just how stable is the inactive conformation ... 

A more detailed understanding of all translocation processes should continue to emerge from genetic and biochemical studies, both in yeasts and In mammals. These studies will undoubtedly reveal additional key proteins Involved In the recognition of targeting sequences and In the translocation of proteins across lipid bIlayers. Finally, the now mostly rudimentary structural studies of translocon channels will likely be extended In the future to reveal the structures and conformational states for the channels at resolutions on the atomic scale. 

Gel phase In lipids, a meso-phase state in which the lipid molecules are tightly packed, diffuse slowly, and sample fewer conformational states. 

Elucidation of the structures of apolipoproteins in the lipid-free state is difficult because they do not have a unique native structure and are conformationally plastic. Spectroscopic... 

Fig. 5. Model of the two-step lipid binding mechanism of apo A Ion a spherical particle [15]. In the lipid-free state in dilute solution, apo A1 is organized into two structural domains in which the N-terminal domain forms a helix bundle whereas the C-terminal domain forms a separate, less organized structure. Initial lipid binding occurs through amphipathic a-helices in the C-terminal domain accompanied by an increase in a-helicity probably in the region including residues 187-220. Subsequently, the helix bundle in the N-terminal domain undergoes a conformational opening, converting hydrophobic helix-helix interactions to helix-lipid interactions.

Both aqueous organic solvent mixtures and differently charged micelles can mimic only roughly the environment of natural cell membranes. In order to analyze in more appropriate model systems possible interactions of gastrin and CCK with cell membranes and to determine their conformational states in lipid bilayers, we have recently investigated in detailed manner this aspect using liposomes. The similarity betwen liposomes and natural membranes is extensively exploited both in vitro and in vivo because of the ability of liposomes to mimic the behaviour of natural membranes. Moreover, the value of liposomes as model membrane systems derives from the fact that they can be constructed with natural constituents. In our approach, we selected as model membranes those formed with the zwitterionic lipids di-myristoylphosphatidylcholine (DMPC) and di-palmitoylphosphatidylcholine (DPPC) as these lipids constitute the major components of most cell membranes. Moreover, in order to operate with a simple system, small unilamellar vesicles (SUVs) were used, i.e. with a diameter between 25 and 250 nm as resulting by rod-type sonication or by extrusion (51). 

As already described in detail in the previous chapters, ion channels are proteins that consist of a few thousand amino acid residues and a few hundred carbohydrate residues that span the lipid cell membrane (I, 2). These channel proteins can have several different three-dimensional structures called conformational states. Some conformational states have a central hole, so that the channel is open to the flow of ions into or out of the cell. Other conformational states are closed to the flow of ions. Because these conformational states differ by energies that are less than the thermal fluctuations, a channel is always spontaneously switching between different open and closed states. 

Most of the reported structural transformations of PC lipid bilayers with respect to environmental conditions such as temperature, pressure, pH, etc., are associated with isomerizations of the constituent lipid molecules (mostly 14—24 carbon acyl chains). For instance, the transition from the ordered gel to fluid liquid crystalline phase, called the main phase transition, has been related to the melting of the hydrocarbon chains in the gel phase, phospholipids with all trans alkyl chains are present, whereas in the disordered liquid crystalline phase the most populated conformational states correspond to gauche forms in the alkyl chains. 

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