Inhibition of the neuraminidase of paramyxoviruses by halide ions: A possible means of modulating the two activities of the HN protein

Merz, David C.; Prehm, Peter; Scheid, Andreas; Choppin, Purnell W.

doi:10.1016/0042-6822(81)90635-8

Cited by 34 publications

(25 citation statements)

References 41 publications

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“…Several studies on monoclonal antibody binding and the sequencing of escape mutants supported two separate sites for HA and NA activities (34). Early studies suggested that a single site was responsible for both functions (31,39). Other studies have suggested that there are two sites in proximity (47), and a kinetic analysis of isolated NDV HN suggested that binding of substrates to an HA site affects the activity of the NA site (38).…”

Section: Discussionmentioning

confidence: 99%

Second Sialic Acid Binding Site in Newcastle Disease Virus Hemagglutinin-Neuraminidase: Implications for Fusion

Zaĭtsev

Itzstein

Groves

et al. 2004

J Virol

163

204

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Paramyxoviruses are the leading cause of respiratory disease in children. Several paramyxoviruses possess a surface glycoprotein, the hemagglutinin-neuraminidase (HN), that is involved in attachment to sialic acid receptors, promotion of fusion, and removal of sialic acid from infected cells and progeny virions. Previously we showed that Newcastle disease virus (NDV) HN contained a pliable sialic acid recognition site that could take two states, a binding state and a catalytic state. Here we present evidence for a second sialic acid binding site at the dimer interface of HN and present a model for its involvement in cell fusion. Three different crystal forms of NDV HN now reveal identical tetrameric arrangements of HN monomers, perhaps indicative of the tetramer association found on the viral surface.

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Section: Discussionmentioning

confidence: 99%

Second Sialic Acid Binding Site in Newcastle Disease Virus Hemagglutinin-Neuraminidase: Implications for Fusion

Zaĭtsev

Itzstein

Groves

et al. 2004

J Virol

163

204

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“…The T193A and H552Q mutants of hPIV3, which have high H (measured as hemadsorption) and wild-type N (measured as cleavage of fluorescent substrate) activity, require exogenous neuraminidase for optimal growth in an airway epithelium model, again suggesting that N must increase to balance the increase in H (10). Although it was originally thought that the different pH optima for binding (pH 7) and neuraminidase activity (approximately pH 5) indicated that the former occurs at the cell surface, while the latter occurs intracellularly (11), these findings suggest that N must also act at the cell surface.…”

mentioning

confidence: 99%

Quantitative Comparison of Human Parainfluenza Virus Hemagglutinin-Neuraminidase Receptor Binding and Receptor Cleavage

Tappert

Porterfield

Mehta-D’souza

et al. 2013

J Virol

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“…In addition, using a 1,1-bis(4-anilino)naphthalene-5,5-disulfonic acid assay, we have recently shown that gangliosides, acting as receptor mimics, did not compete with N-acetylneuraminic acid for binding (Ferreira et al, 2004), although both provoked a conformational change in the HN protein. Nevertheless, early papers suggested that a single site could be responsible for both functions (Scheid & Choppin, 1974;Merz et al, 1981), whereas other studies have suggested the close proximity of the two sites (Thompson & Portner, 1987). In this sense, based on their X-ray data of the globular head of the HN protein (lacking the first 123 residues of the N-terminal portion of the polypeptide), Crennell et al (2000) suggested the existence of a unique, interchangeable site with two states, a sialic acid-binding state and a catalytic state.…”

Section: Resultsmentioning

confidence: 99%

Sialidase, receptor-binding and fusion-promotion activities of Newcastle disease virus haemagglutinin–neuraminidase glycoprotein: a mutational and kinetic study

Ferreira

Muñoz-Barroso

Marcos

et al. 2004

Journal of General Virology

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Mutations were generated in residues at the putative catalytic site of the haemagglutinin-neuraminidase (HN) protein of Newcastle disease virus Clone 30 strain (Arg498, Glu258, Tyr262, Tyr317 and Ser418) and their effects on its three associated activities were studied. Expression of the mutant proteins at the surface of HeLa cells was similar to that of the wild-type. Sialidase, receptor-binding and fusion-promotion activities were affected to different degrees for all mutants studied. Mutant Arg498Lys lost most of its sialidase activity, although it retained most of the receptor-binding activity, suggesting that, for the former activity, besides the presence of a basic residue, the proximity to the substrate molecule is also important, as Lys is shorter than Arg. Proximity also seems to be important in substrate recognition, since Tyr262Phe retained most of its sialidase activity while Tyr262Ser lost most of it. Also, Ser418Ala displayed most of the wild-type sialidase activity. However, a kinetic and thermodynamic study of the sialidase activity of the Tyr262Ser and Ser418Ala mutants was performed and revealed that the hydroxyl group of these residues also plays an important role in catalysis, since such activity was much less effective than that of the wild-type and these mutations modified their activation energy for sialidase catalysis. The discrepancy of the modifications in sialidase and receptor-binding activities in the mutants analysed does not account for the topological coincidence of the two sites. These results also suggest that the globular head of HN protein may play a role in fusion-promotion activity. INTRODUCTIONMembers of the family Paramyxoviridae such as Newcastle disease virus (NDV) are enveloped, negative-strand RNA viruses that encode two transmembrane glycoproteins: an attachment protein and a fusion protein. The attachment protein, the haemagglutinin-neuraminidase (HN) or sialidase, interacts with sialic acid located at the termini of host glycoconjugates through its haemadsorption (HAd) activity. Moreover, HN possesses sialidase activity to hydrolyse sialic acid residues from progeny virion particles to prevent virus self-aggregation (Lamb & Kolakofsky, 2001). In addition to these activities, the HN protein also displays a fusion-promotion activity.HN is a type-II protein with a single transmembrane segment having a terminal globular head in which HAd and sialidase activities reside, together with residues probably involved in fusion promotion. The structure of the HN protein displays the six-bladed b-propeller fold typical of other known sialidases (Varghese et al., 1983;Crennell et al., 1993Crennell et al., , 1994Crennell et al., , 2000Gaskell et al., 1995; Sagrera et al., 2001). Recently, the crystal structure of the NDV HN globular head has been determined, both alone and complexed with the inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Crennell et al., 2000), revealing an active site that shares many features with other sialidases: (i) a triarginyl cluster (Arg174, Arg41...

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Inhibition of the neuraminidase of paramyxoviruses by halide ions: A possible means of modulating the two activities of the HN protein

Cited by 34 publications

References 41 publications

Second Sialic Acid Binding Site in Newcastle Disease Virus Hemagglutinin-Neuraminidase: Implications for Fusion

Second Sialic Acid Binding Site in Newcastle Disease Virus Hemagglutinin-Neuraminidase: Implications for Fusion

Quantitative Comparison of Human Parainfluenza Virus Hemagglutinin-Neuraminidase Receptor Binding and Receptor Cleavage

Sialidase, receptor-binding and fusion-promotion activities of Newcastle disease virus haemagglutinin–neuraminidase glycoprotein: a mutational and kinetic study

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