Membrane protein activity, bilayer

Gruner SM. Coupling between bilayer curvature elasticity and membrane-protein activity. In Biomembrane Electrochemistry, Volume 235. Blank M, Vodyanoy I, eds. 1994. American Chemical Society, Washington, DC. pp. 129-149. 

The lipid bilayer is not passive in determining membrane protein activity and function, and an accumulating body of evidence indicates that there is a coupling of membrane proteins to lipid bilayer properties. These properties include the effect of bilayer curvature strain (20), the role of specific lipids such as phosphoinositides, (21) and the effect of thickness on membrane protein function (22). The lipid composition, as well as the bilayer properties that result from this composition, act as allosteric regulators of membrane protein function. 

Relatively large changes in membrane thickness have been demonstrated to alter the function of integral membrane proteins. An example of the magnitude of the change in membrane thickness needed to alter protein function is provided by studies of the sarcoplasmic reticulum calcium ATPase. Activity of this integral membrane protein in bilayers with symmetrically substituted, monounsaturated acyl chains with 16, 18, or 20 carbons is nearly constant. However, when the acyl chains are shortened to 14 carbons or lengthened to 22 carbons, activity is reduced by more than a factor of 3 (Lee, 1998). 

Coupling between Bilayer Curvature Elasticity and Membrane Protein Activity... 

Carruthers, A. and Melchior, D.L. (1986) How bilayer lipids affect membrane protein activity. Trends Biochem. ScL, 11, 331-335. 

The primary site of action is postulated to be the Hpid matrix of cell membranes. The Hpid properties which are said to be altered vary from theory to theory and include enhancing membrane fluidity volume expansion melting of gel phases increasing membrane thickness, surface tension, and lateral surface pressure and encouraging the formation of polar dislocations (10,11). Most theories postulate that changes in the Hpids influence the activities of cmcial membrane proteins such as ion channels. The Hpid theories suffer from an important drawback at clinically used concentrations, the effects of inhalational anesthetics on Hpid bilayers are very small and essentially undetectable (6,12,13). 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Indeed, hydrophilic N- or C-terminal ends and loop domains of these membrane proteins exposed to aqueous phases are able to undergo rapid or intermediate motional fluctuations, respectively, as shown in the 3D pictures of transmembrane (TM) moieties of bacteriorhodopsin (bR) as a typical membrane protein in the purple membrane (PM) of Halobacterium salinarum.176 178 Structural information about protein surfaces, including the interhelical loops and N- and C-terminal ends, is completely missing from X-ray data. It is also conceivable that such pictures should be further modified, when membrane proteins in biologically active states are not always present as oligomers such as dimer or trimer as in 2D or 3D crystals but as monomers in lipid bilayers. 

Membrane proteins lower the activation energy for transport of polar compounds and ions by providing an alternative path through the bilayer for specific solutes. Proteins that bring about this facilitated diffusion, or passive transport, are not enzymes in the usual sense their substrates are moved from one compartment to another, but are not chemically altered. Membrane proteins that speed the movement of a solute across a membrane by facilitating diffusion are called transporters or permeases. 

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