Protein-lipid interactions selectivity

Biological membranes are always pictured as being very selective barriers separating different biochemical reaction compartments. This high performance transport specificity solely depends on the presence of membrane proteins embedded in the lipid matrix. On the other hand, most membrane proteins cease to function in the absence of lipids. In order to introduce biological transport abilities into artificial membrane systems protein-lipid interactions are of vital interest. The question is how the activity of membrane proteins is affected if they are placed into a polymeric environment. 

The structure of this water-selective membrane pore protein (Fig. 3a and 3b) represents the highest resolution stmcture obtained from electron crystallography to date (53). Data were obtained for Aquaporin-O in double-layered 2-D crystals, and its staggering 1.9-A resolution clearly reveals water molecules within the pore. The data also reveal associated lipids, allowing key protein-lipid interactions to be modeled. 

This review will focus on a combination of molecular genetic and biochemical studies on the role of primarily phosphatidylethanolamine (PE) and cardi-olipin (CL) in the folding and organization of individual membrane proteins and multicomponent supercomplexes. The results of such studies will be related to the known and possible involvement of lipids in diseases resulting from lack of proper organization of membrane proteins. Rather than being an inclusive review of protein-lipid interactions, the aim is to select specific well-documented examples of lipid-protein interactions to illustrate the broader role of lipids in determining cellular function. 

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. 

Cellular membranes function as selective barriers and integral membrane protein scaffolds. Membranes allow the compartmentalization of cells, and individual organelles within cells, and are critical in energy transduction and cell signaling. In vivo membranes contain hundreds to thousands of lipid types, making characterization of particular lipid-lipid interactions challenging. 

The interaction between biological macromolecules can be of various degrees of complexity. These interactions may be of high specificity, as in antigen-antibody complexes, or of low specificity, as in protein-lipid associations. The complexes that are formed may be very stable, or highly unstable. These properties of a complex must be considered in selecting an affinity adsorbent to be used for the purification of a specific substance. 

In view of the complexity and diversity of the functions performed by the various proteins embedded in a biomembrane (the integral proteins), it has been found convenient to incorporate single integral proteins or smaller lipophihc biomolecules into experimental models of biological membranes, so as to isolate and investigate their functions. This serves to reduce complex membrane processes to well-defined interactions between selected proteins, lipids, and hgands. There is... 

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