Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , , |
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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Brazilian Journal of Infectious Diseases |
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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 |
_version_ |
1754209240686264320 |