Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein

Detalhes bibliográficos
Autor(a) principal: Santos-López,Gerardo
Data de Publicação: 2009
Outros Autores: Scior,Thomas, Borraz-Argüello,María del Tránsito, Vallejo-Ruiz,Verónica, Herrera-Camacho,Irma, Tapia-Ramírez,José, Reyes-Leyva,Julio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Infectious Diseases
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000100007
Resumo: A point mutation from guanine (G) to adenine (A) at nucleotide position 1081 in the hemagglutinin-neuraminidase (HN) gene has been associated with neurovirulence of Urabe AM9 mumps virus vaccine. This mutation corresponds to a glutamic acid (E) to lysine (K) change at position 335 in the HN glycoprotein. We have experimentally demonstrated that two variants of Urabe AM9 strain (HN-A1081 and HN-G1081) differ in neurotropism, sialic acidbinding affinity and neuraminidase activity. In the present study, we performed a structure-function analysis of that amino acid substitution; the structures of HN protein of both Urabe AM9 strain variants were predicted. Based on our analysis, the E/K mutation changes the protein surface properties and to a lesser extent their conformations, which in turn reflects in activity changes. Our modeling results suggest that this E/K interchange does not affect the structure of the sialic acid binding motif; however, the electrostatic surface differs drastically due to an exposed short alpha helix. Consequently, this mutation may affect the accessibility of HN to substrates and membrane receptors of the host cells. Our findings appear to explain the observed differences in neurotropism of these vaccine strains.
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spelling Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase proteinHemagglutinin-neuraminidasamumps virusparamyxovirus3D structure predictionsialic acidA point mutation from guanine (G) to adenine (A) at nucleotide position 1081 in the hemagglutinin-neuraminidase (HN) gene has been associated with neurovirulence of Urabe AM9 mumps virus vaccine. This mutation corresponds to a glutamic acid (E) to lysine (K) change at position 335 in the HN glycoprotein. We have experimentally demonstrated that two variants of Urabe AM9 strain (HN-A1081 and HN-G1081) differ in neurotropism, sialic acidbinding affinity and neuraminidase activity. In the present study, we performed a structure-function analysis of that amino acid substitution; the structures of HN protein of both Urabe AM9 strain variants were predicted. Based on our analysis, the E/K mutation changes the protein surface properties and to a lesser extent their conformations, which in turn reflects in activity changes. Our modeling results suggest that this E/K interchange does not affect the structure of the sialic acid binding motif; however, the electrostatic surface differs drastically due to an exposed short alpha helix. Consequently, this mutation may affect the accessibility of HN to substrates and membrane receptors of the host cells. Our findings appear to explain the observed differences in neurotropism of these vaccine strains.Brazilian Society of Infectious Diseases2009-02-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000100007Brazilian Journal of Infectious Diseases v.13 n.1 2009reponame:Brazilian Journal of Infectious Diseasesinstname:Brazilian Society of Infectious Diseases (BSID)instacron:BSID10.1590/S1413-86702009000100007info:eu-repo/semantics/openAccessSantos-López,GerardoScior,ThomasBorraz-Argüello,María del TránsitoVallejo-Ruiz,VerónicaHerrera-Camacho,IrmaTapia-Ramírez,JoséReyes-Leyva,Julioeng2009-06-30T00:00:00Zoai:scielo:S1413-86702009000100007Revistahttps://www.bjid.org.br/https://old.scielo.br/oai/scielo-oai.phpbjid@bjid.org.br||lgoldani@ufrgs.br1678-43911413-8670opendoar:2009-06-30T00:00Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID)false
dc.title.none.fl_str_mv Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
title Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
spellingShingle Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
Santos-López,Gerardo
Hemagglutinin-neuraminidasa
mumps virus
paramyxovirus
3D structure prediction
sialic acid
title_short Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
title_full Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
title_fullStr Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
title_full_unstemmed Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
title_sort Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
author Santos-López,Gerardo
author_facet Santos-López,Gerardo
Scior,Thomas
Borraz-Argüello,María del Tránsito
Vallejo-Ruiz,Verónica
Herrera-Camacho,Irma
Tapia-Ramírez,José
Reyes-Leyva,Julio
author_role author
author2 Scior,Thomas
Borraz-Argüello,María del Tránsito
Vallejo-Ruiz,Verónica
Herrera-Camacho,Irma
Tapia-Ramírez,José
Reyes-Leyva,Julio
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Santos-López,Gerardo
Scior,Thomas
Borraz-Argüello,María del Tránsito
Vallejo-Ruiz,Verónica
Herrera-Camacho,Irma
Tapia-Ramírez,José
Reyes-Leyva,Julio
dc.subject.por.fl_str_mv Hemagglutinin-neuraminidasa
mumps virus
paramyxovirus
3D structure prediction
sialic acid
topic Hemagglutinin-neuraminidasa
mumps virus
paramyxovirus
3D structure prediction
sialic acid
description A point mutation from guanine (G) to adenine (A) at nucleotide position 1081 in the hemagglutinin-neuraminidase (HN) gene has been associated with neurovirulence of Urabe AM9 mumps virus vaccine. This mutation corresponds to a glutamic acid (E) to lysine (K) change at position 335 in the HN glycoprotein. We have experimentally demonstrated that two variants of Urabe AM9 strain (HN-A1081 and HN-G1081) differ in neurotropism, sialic acidbinding affinity and neuraminidase activity. In the present study, we performed a structure-function analysis of that amino acid substitution; the structures of HN protein of both Urabe AM9 strain variants were predicted. Based on our analysis, the E/K mutation changes the protein surface properties and to a lesser extent their conformations, which in turn reflects in activity changes. Our modeling results suggest that this E/K interchange does not affect the structure of the sialic acid binding motif; however, the electrostatic surface differs drastically due to an exposed short alpha helix. Consequently, this mutation may affect the accessibility of HN to substrates and membrane receptors of the host cells. Our findings appear to explain the observed differences in neurotropism of these vaccine strains.
publishDate 2009
dc.date.none.fl_str_mv 2009-02-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000100007
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1413-86702009000100007
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S1413-86702009000100007
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Brazilian Society of Infectious Diseases
publisher.none.fl_str_mv Brazilian Society of Infectious Diseases
dc.source.none.fl_str_mv Brazilian Journal of Infectious Diseases v.13 n.1 2009
reponame:Brazilian Journal of Infectious Diseases
instname:Brazilian Society of Infectious Diseases (BSID)
instacron:BSID
instname_str Brazilian Society of Infectious Diseases (BSID)
instacron_str BSID
institution BSID
reponame_str Brazilian Journal of Infectious Diseases
collection Brazilian Journal of Infectious Diseases
repository.name.fl_str_mv Brazilian Journal of Infectious Diseases - Brazilian Society of Infectious Diseases (BSID)
repository.mail.fl_str_mv bjid@bjid.org.br||lgoldani@ufrgs.br
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