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Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
- Source :
- Brazilian Journal of Infectious Diseases v.13 n.1 2009, Brazilian Journal of Infectious Diseases, Brazilian Society of Infectious Diseases (BSID), instacron:BSID, Scopus-Elsevier, Brazilian Journal of Infectious Diseases, Vol 13, Iss 1, Pp 24-34, Brazilian Journal of Infectious Diseases, Volume: 13, Issue: 1, Pages: 24-34, Published: FEB 2009
- Publication Year :
- 2009
- Publisher :
- Brazilian Society of Infectious Diseases, 2009.
-
Abstract
- 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.
- Subjects :
- Microbiology (medical)
lcsh:QR1-502
Mumps Vaccine
Sialic acid binding
Mumps virus
Biology
Sialidase
medicine.disease_cause
lcsh:Microbiology
lcsh:Infectious and parasitic diseases
chemistry.chemical_compound
Structure-Activity Relationship
paramyxovirus
Cell Line, Tumor
Chlorocebus aethiops
medicine
Animals
Humans
Point Mutation
3D structure prediction
lcsh:RC109-216
HN Protein
Vero Cells
Point mutation
Hemagglutinin-neuraminidasa
Genetic Variation
Sialic acid
Infectious Diseases
chemistry
Biochemistry
Amino Acid Substitution
sialic acid
mumps virus
Hemagglutinin-neuraminidase
Alpha helix
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Brazilian Journal of Infectious Diseases v.13 n.1 2009, Brazilian Journal of Infectious Diseases, Brazilian Society of Infectious Diseases (BSID), instacron:BSID, Scopus-Elsevier, Brazilian Journal of Infectious Diseases, Vol 13, Iss 1, Pp 24-34, Brazilian Journal of Infectious Diseases, Volume: 13, Issue: 1, Pages: 24-34, Published: FEB 2009
- Accession number :
- edsair.doi.dedup.....4a2a5b1f1cf9cabb63f10ffaff3da3b2