Intrinsic membrane protein

Cyanobacteria, prokaryotic algae that perform oxygenic photosynthesis, respond to a decrease in ambient growth temperature by desaturating the fatty acids of membrane lipids to compensate for the decrease in the molecular motion of the membrane lipids at low temperatures. During low-temperature acclimation of cyanobacterial cells, the desaturation of fatty acids occurs without de novo synthesis of fatty acids [110, 111]. All known cyanobacterial desaturases are intrinsic membrane proteins that act on acyl-Hpid substrates. 

The Ca transport ATPase of sarcoplasmic reticulum is an intrinsic membrane protein of 110 kDa [8-11] that controls the distribution of intracellular Ca by ATP-dependent translocation of Ca " ions from the cytoplasm into the lumen of the sarcoplasmic reticulum [12-16],... 

With active transport, energy is expended to move a substance against its concentration gradient from an area of low concentration to an area of high concentration. This process is used to accumulate a substance on one side of the plasma membrane or the other. The most common example of active transport is the sodium-potassium pump that involves the activity of Na+-K+ ATPase, an intrinsic membrane protein. For each ATP molecule hydrolyzed by Na+-K+ ATPase, this pump moves three Na+ ions out of the cell and two K+ ions into it. As will be discussed further in the next chapter, the activity of this pump contributes to the difference in composition of the extracellular and intracellular fluids necessary for nerve and muscle cells to function. 

The adult nicotinic acetylcholine receptor (nAChR) is an intrinsic membrane protein with five distinct subunits (a2B T). A Cartoon of the one of five subunits of the AChR in the end plate surface of adult mammalian muscle. Each subunit contains four helical domains labeled Ml to M4. The 2 domains line the channel pore. B Cartoon of the full nAChR. The N termini of two subunits cooperate to form two distinct binding pockets for acetylcholine (ACh). These pockets occur at the (X-B and the 3-Ct subunit interfaces. 

Opsin is an intrinsic membrane protein with a molecular weight of about 38,000. It accounts for about 95% of the protein in the disk membranes. The carboxyl-terminal end... 

Complexes of intrinsic membrane proteins and lipids can form hydrophilic or hydro-phobic channels that allow transport of molecules with different physicochemical characteristics. The amphipathic nature of the membrane creates a barrier for ionized, highly polar drugs, although it does not completely exclude them. The presence of pores of approximately 4 A are believed to allow for ready movement of small molecules such as water. Thus certain molecules that ordinarily would be excluded can rapidly traverse the highly lipid membrane barrier. 

Whitelegge, J. P. Gundersen, C. B. Faull, K. F. 1998. Electrospray-ionization mass spectrometry of intact intrinsic membrane proteins. Protein Sci., 7,1423-1430. 

Fig. 1.3 Classes of intrinsic membrane proteins, as defined by Blobel [29]. The peptides chains end in amino (N) and carboxy (C) termini. The disposition of the N- and C-termini differs for each class of membrane protein, only two membrane spannings are indicated for the polytopic class however, the number of membrane spannings is not limited for polytopic membrane proteins. (Reprinted from Fig. 1 of ref. 30 with permission from CRC Press.)...

The objective of this study was also to establish a link between an easily observable allelopathic effect (growth inhibition of roots) and a cellular-based explanation (membrane permeability changes). Several modes of action can explain these results, such as an increase in the lipid peroxidation, a disruption in the intrinsic membrane protein activities, or an alteration in plasma membrane ATPase activity. 

Thus, according to this hydrophobicity hypothesis , proteins that are encoded and synthesised within organelles are characterised by shared, and extreme, hydrophobicity - all are intrinsic membrane proteins (Claros et al. 1995 Popot and de Vitry 1990 Von Heijne 1986). 

Figure 9.25 The transferrin receptor, an intrinsic membrane protein. (Reproduced by permission from Newman R, Schneider C, Sutherland R, et al. The transferrin receptor. Trends Biochem Sci November 397-400, 1982.)...

Not all proteins can be crystallized. This is especially true of intrinsic membrane proteins which need to be solubilized in the presence of detergents. 

Since the 28K-proacrosin interaction required either 8 M urea or 6 M guanidine HC1 to disrupt it (10), this protein-protein interaction may act to anchor proacrosin to the acrosomal membranes or to other proacrosin molecules. While acrosin does not fit all the criteria for an intrinsic membrane protein, acrosin was associated with and extracted from preparations of sperm membrane vesicles with 1 mM HC1 and Triton X-100 (5 , Urch, unpublished observations). Salt or combinations of salt and detergent were ineffective. The interaction of acrosin with membranes, particularly sperm acrosomal membranes, is obviously important in ZP binding and penetration. 

Protein-membrane association via a post-translational modification introduces the notion of dynamic association and partitioning of proteins between the membrane phase of the cells and the aqueous phase (cytosol or inner phase of organelles). Consequently, such proteins can be found both as membrane-associated and membrane-free, which is not the case with intrinsic membrane proteins which are strictly membrane embedded. Another type of association to membrane is mediated by protein-protein interactions with other membrane proteins. A typical example of this situation is provided by the respiratory complexes. In the case of ubiquinol-cytochrome c oxidoreductase, core proteins 1 and 2 does not show any interaction with the lipid membrane, but only with the protein subunits spanning the membrane (e.g. cytochrome b) (Iwata et al. 1998). 

The N-terminal amino acid sequence of both of these polypeptides has been determined [11,12]. Polypeptides of 7, 6.5, 5.5 and 5 kDa have been shown to be associated with a spinach PS II preparation [13]. The three larger polypeptides are hydrophobic, as shown by partitioning in Triton X-114, and are presumed to be intrinsic membrane proteins. The 5 kDa polypeptide is hydrophilic and therefore presumably peripheral to the core complex. This polypeptide has been purified and its amino acid composition determined [13]. 

Figure 12.28. Hydropathy Plot for Porin. No strong peaks are observed for this intrinsic membrane protein because it is constructed from membrane-spanning P strands rather than a helices.

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