Cell membrane primary structure

The basement membrane is a structure that supports overlying epithelial or endothelial cells. The primary fimction of the basement membrane is to anchor down the epithelium to its loose connective tissue underneath. This is achieved by cell-matrix adhesions through cell adhesion molecules. 

Next, Reilly et al. [65] localized the Na /H exchanger gene product in renal epithelial cells where the distributions of the kinetic isoforms was well-established. The strategy was based on the observation that the resistant- and sensitive-types are restricted to the apical and basolateral membranes, respectively, in confluent LLC-PK]/Clone 4 cells [8]. Thus, if proteins encoded by the cloned cDNAs localized to the apical membrane this would indicate that they represent the resistant-type. Localization to the basolateral membrane would prove they were the sensitive-type and presence on both membranes would suggest that the two functional isoforms had identical primary structures. Na exchanger proteins were localized by... 

The transmembrane domain in the RPTK is a hydrophobic segment of 22-26 amino acids inserted in the cell membrane. It is flanked by a proline-rich region in the N-terminus and a cluster of basic amino acids in the C-ter-minus. This combination of structures secures the transmembrane domain within the lipid bilayer. There is a low degree of homology in the transmembrane domain, even between two closely related RPTKs, suggesting that the primary sequence contains little information for signal transduction. 

Type XXVIII collagen belongs to the class of VWA domain-containing proteins. The primary structure is similar to type VI collagen. It is mainly a component of the basement membranes around Schwann cells in the peripheral nervous system. ... 

The abnormal deposits found in the brains of CJD victims consist of an abnormal isoform of PrP. Prion protein is normally found in cells. Detailed structural studies show that normal cellular PrP (PrP ) is a soluble protein whose conformation is rich in a-helices with very little P-sheet. The PrP protein extracted from the brains of CJD victims (i.e., PrP ) is identical in primary amino acid sequence to the normal PrP (PrP ). However, PrP has a much greater content of P-sheet conformation with little a-helical structure. Thus PrP is neurotoxic because of its three-dimensional structure. When the prion protein is predominantly in an a-helical conformation it is nontoxic when the prion protein is predominantly in a P-sheet conformation, it kills neurons. The prion protein is thus made neurotoxic not by its amino acid composition but by its conformation. This concept is both fascinating and terrifying. Prion diseases are transmissible thus prions are infectious agents. However, prions are not like bacteria or viruses, or other infectious microbes—they are simply protein molecules. Prions are not microbes with cell membranes and nucleic acids they are not living things. Indeed, prions are not even infectious molecules, they are infectious molecular shapes. 

The efficiency of complex treatment in many cases depends on the protection level of the structure and function of cell membranes. For correction of these disorders a complex of measures, including antioxidative and enterosorption preparations, was used. By chemical binding of heavy metals pectin enterosorbent ensures fast elimination of the primary source of intoxication. 

Fig. 5.6. Topology of the P-adrenergic receptor of hamster. The primary structure is shown of the P-receptor for adrenaline from hamster, with the assumed topology of the seven transmembrane helices. The extracellular domain is shown at the top of the picture. The interface of the ceU membrane is indicated by the dashed line. The filled squares show glycosylation sites. Amino adds not required for ligand binding, according to mutagenesis studies, are shown as open squares. Reprinted with permission of the American Journal of Respiratory Cell and Molecular Biology (1989), 1, No.2, p.82.

The hepatocytes was subcultured for 2 days and their albumin secretion activity was measured. The TRS-harvested hepatocytes showed nearly the same albumin secretion activity as the primary culture, whereas the ERS-harvested ones showed only 20% activity. This finding is important because no subculture of hepatocyte has ever been successful, owing to a possible proteolytic disruption of cell-membrane structure (especially cell-cell adhesion) in the course of trypsin treatment. 

The plasma lipoproteins contain eight major apoproteins, the structure and function of which have recently been reviewed (5). Briefly, the primary amino acid sequence is known for five of these apoproteins. ApoB, a highly hydrophobic protein, is found in chylomicrons, VLDL and LDL. It is the major polypeptide in LDL and has been shown to be responsible, in part, for the recognition of LDL by its receptor in cultured human fibroblasts (7,10). The major polypeptides of HDL are apoA-I and apoA-II apoA-l activates lecithin cholesterol acyl transferase. In addition, studies on the cellular level suggest that apoA-I may regulate the content of the lipids in the cell membrane (8). 

Based on previous works on Homeopathy we have hypothesized that the primary target of a homeopathic potency in an organism is the water-channel protein or aquaporin (Sukul and Sukul, 2001). Aquaporins occur in all life forms and facilitate permeation of water across biological membranes. We have discussed in details about the structure and function of aquaporins and their relation to health and disease in chapter IV. There are several types of aquaporins (AQP) and one type AQP1 occurs abundantly in red blood cells of vertebrates. If the primary target of a homeopathic potency is aquaporin, application of a homeopathic potency on cell membranes would affect water flow into the cells. In order to test this hypothesis we treated red blood cells of a fresh water fish (Clarius batrachus) with Mercuric chloride 30 (Merc cor 30) and Nux vomica 30 (Nux vom 30) separately in a hypotonic medium. In the control red cells were treated with Ethanol 30. The diluent medium in all the three potencies consisted of 90% ethanol and 10% distilled water. 

The primary method for determining protein structure is x-ray crystallography. Unfortunately, the receptors most frequently targeted by the pharmaceutical industry are embedded in cell membranes. The cell membrane plays a vital role in determining the overall shape of a membrane-bound receptor. Crystallization is performed in the absence of membrane lipids, so x-ray information is not representative of the true receptor structure. Therefore, reliable structural information on receptors is difficult to obtain. 

The barrier properties of human skin have long been an area of multidisciplinary research. Skin is one of the most difficult biological barriers to penetrate and traverse, primarily due to the presence of the stratum corneum. The stratum cor-neum is composed of comeocytes laid in a brick-and-mortar arrangement with layers of lipid. The corneocytes are partially dehydrated, anuclear, metabolically active cells completely filled with bundles of keratin with a thick and insoluble envelope replacing the cell membrane [29]. The primary lipids in the stratum corneum are ceramides, free sterols, free fatty acids and triglycerides [30], which form lamellar lipid sheets between the corneocytes. These unique structural features of the stratum comeum provide an excellent barrier to the penetration of most molecules, particularly large, hydrophilic molecules such as ASOs. 

Fig. 5. Schematic diagram summarizing the available structural information on the Halobacterium cell envelope from X-ray studies of the envelopes (Blaurock el al., 1976), from the primary structure of the surface glycoprotein (Lechner and Sumper, 1987), and from the three-dimensional structure described by Kessel el al. (1988). The three-dimensional structure determined by electron microscopy depicts only the upper dome-shaped region of the structure, which is separated from the cell membrane by the spacer elements. As indicated by the crystallographic symbols, the section runs from sixfold to sixfold axis via the twofold axis. From Kessel et al., (1988), with permission.

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