Annular lipids

In a biological membrane, lipid molecules are generally considered to act as solvent for integral proteins, just like water smroimds soluble compoimds in solution. In this lipid-solvent model, the lipids are loosely attached to the protein and thus can be easily displaced by other membrane lipids (Fig. 6.2). These "solvent" lipids have been referred to as annular lipids, because they form an annular shell of lipids aroimd the protein. Protein-lipid interactions of this type are relatively nonspecific. Qn the other hand, some proteins interact with a high specificity with selected lipid molecules, such as cholesteroP or sphingolipids. In this case, these lipids are referred to as "nonaimular." Nonaimular lipids may act as cofactors that control the biological activity of the protein through conformational effects. 

Finally, membrane lipids that do not physically interact with a protein are referred to as bulk lipids, usually phosphatidylcholine. These bulk glycerophospholipids can take the place of annular lipids via a rapid exchange mechanism (estimated to 10 s at 37°C)P The rate of exchange of nonannular lipids with bulk lipids is presumed to be significantly slower, given the high affinity of the protein for its nonaimular lipid cofactors. In this chapter, we will review the different mechanisms involved in the specific interaction of membrane proteins with nonannular lipids. 

FIGURE 6.2 Annular vs. nonannular lipids. Annular lipids (left panel) form an annular shell of lipids that are loosely attached to the protein. These lipids act as "solvent" in the bidimensional plane of the membrane and are easily exchangeable with surrounding bulk lipids (green disks). Nonannular lipids (blue disks) interact more strongly with membrane proteins and are not exchangeable with bulk lipids. Cholesterol and sphingoUpids are typical nonannular lipids, whereas phosphatidylcholine is a representative annular lipid. 

East JM, Melville D, Lee AG. Exchange rates and numbers of annular lipids for the calcium and magnesium ion dependent adenosinetriphosphatase. Biochemistry. 1985 24(ll) 2615-2623. 

Concerning the nature and structure of such amyloid peptide or protein channels, oligomers with annular morphologies have in fact been observed by EM for a-synuclein (Lashuel et al., 2002) and equine lysozyme (Malisauskas et al., 2003) even in the absence of any lipids or membranes. Channel-like structures have also been reconstituted in liposomes and observed by SFM for A/ i 4o, A/ j 42, human amylin, a-synuclein, ABri, ADan, and serum amyloid A (Fig. 5A Lin et al., 2001 Quist et al., 2005). Doughnut-shaped structures with a diameter of 10-12 nm and a central hole size of 1-2 nm (Fig. 5B) were imaged on top of lipid membranes (Quist et al., 2005). However, the radius of curvature of the SFM tips meant that it is not possible to say whether the pores were really traversing the lipid bilayer. 

Figure 5. A cross section through a Hz/ phase that illustrates that the interstitial areas (stipled) break the axial symmetry of the Hu tubes. The water cores (hatched) are in the center. A few lipids are shown in the leftmost cylinder for orientation. Lipid hydrocarbon chains fill the interstitial as well as the annular regions. Deviations from the mean hydrocarbon chain-segment density or in the mean extended length of the chains correspond to an entropically expensive set of chain configurations.

The sequence of events that leads extracellular disordered a-synuclein monomers to form highly organized annular channels in fhe plasma membrane of brain cells is summarized in Fig. 10.10. The firsf sfep is the attraction of a-synuclein by lipid rafts microdomains for which fhe protein has a marked preference over more fluid regions of fhe membrane eraiched in phosphatidylcholine. Once boimd to the surface of lipid rafts, the protein will definitively adopt a a-helical structure with a central turn domain containing the SBD. 

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