Neuraminidase membrane binding

Influenza virus particles are spheroidal and approximately 100 nm in diameter. The outer-membrane envelope contains 500 copies of hemagglutinin (HA) trimers and 100 copies of neuraminidase tetramers. The hemagglutinin constitutes the receptor sites for a-sialoside ligands. X-ray analyses show that the three sialic acid binding pockets reside 46 A apart, each trimer being separated on the virion surface by about 65-110 A [42],... 

The existence of specific receptors for transferrin on the reticulocyte membrane was implied by the work of Jandl and associates, who observed that trypsin virtually abolished the ability of reticulocytes to take up iron from transferrin without affecting other metabolic functions of the cells (8). Whether the effect of the enzyme was to cleave the receptor from the cell membrane or to degrade it proteolytically was not clear. Neuraminidase treatment also depressed iron uptake by reticulocytes, but to a much lesser degree than trypsin and only at much higher concentrations than needed to abolish the hemagglutinating effects of influenza virus. Subsequent work from Morgan s laboratory has confirmed these results and has shown further that binding of transferrin to the receptor protects it from proteolytic enzymes (70). 

Animal V. The first stage of infection is adsorption of the vims to the exterior surface of the animal cell membrane. Adsorption occurs by interaction between a virus-coded protein on the surface of the virion and a receptor moleeule on the cell membrane. Most cell receptors are glycoproteins. Moreover, they are normal membrane glycoproteins with specific functions unrelated to virus infection. The interaction is specific. Thus, the binding protein of influenza virus interacts with the o2 3 linked terminal sialic add residue of the host cell membrane glycopFOtein treatment of a cell with sialidase (neuraminidase) renders it resistant to infection, and glycoproteins with al 6 linked siaUc acid do not serve as receptors. Under natural conditions, the presence of appropriate receptor molecules on the cell membrane is a precondition for virus infection, i.e. in the absence of receptors, the cell is not permissive for virus infection... 

The amoeba Acanthamoeba castellani has been shown to bind to equine erythrocytes by interaction with carbohydrates on the surface of the red cells. 4-Nitrophenyl tri-A-methyltyrosinate [ I]iodide has been used to label the outer surface of mature chicken erythrocytes. Two component glycoproteins, with subunits of molecular weight 5 x 10 and 1 x 10 , were identified. Neuraminidase-treated rat and rabbit erythrocytes were shown to be rapidly sequestered by the liver. Chemical studies of glycoproteins obtained from erythrocyte membranes from a number of sources have been reported. ... 

Influenza vims A has two surface glycoproteins that offer potential for the development of competitive multivalent sugar clusters featuring 5-A -acetyl neuraminic acid (Neu5Ac) units [35]. Haemagglutinin (HA) binds to sialic acid receptors and fuses the cell membranes of the vims and host and neuraminidase (NA), an enzyme, cleaves sialic acid residues and is involved in release of new vims by the host cell. Whilst small molecule inhibitors of NA, such as oseltamivir (Tamiflu) and zanamavir (Relenza), are now available, no therapy based on inhibition of binding of HA has reached the clinic. 

The resistance of cells to lysis by antibodies and complement can be removed by treating the cells with neuraminidase. Glycoproteins have been shown to participate in binding Ca + ions to, and in transporting Ca + ions across, mitochondrial membranes. Removal of sialic acid residues from the surface of cultured heart cells increased the ability of the cells to exchange Ca " ions, but that of K+ ions was unaffected. Glycoproteins on the surface of human KB cells are involved in binding adenovirus. ... 

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