6JJM

Crystal structure of Mumps virus hemagglutinin-neuraminidase bound to the oligosaccharide portion of the GM2 ganglioside


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.184 

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Literature

Molecular Mechanism of the Flexible Glycan Receptor Recognition by Mumps Virus.

Kubota, M.Matsuoka, R.Suzuki, T.Yonekura, K.Yanagi, Y.Hashiguchi, T.

(2019) J Virol 93

  • DOI: https://doi.org/10.1128/JVI.00344-19
  • Primary Citation of Related Structures:  
    6JJM, 6JJN

  • PubMed Abstract: 

    Mumps virus (MuV) is an important aerosol-transmitted human pathogen causing epidemic parotitis, meningitis, encephalitis, and deafness. MuV preferentially uses a trisaccharide containing α2,3-linked sialic acid as a receptor. However, given the MuV tropism toward glandular tissues and the central nervous system, an additional glycan motif(s) may also serve as a receptor. Here, we performed a large-scale glycan array screen with MuV hemagglutinin-neuraminidase (MuV-HN) attachment proteins by using 600 types of glycans from The Consortium for Functional Glycomics Protein-Glycan Interaction Core in an effort to find new glycan receptor motif(s). According to the results of the glycan array, we successfully determined the crystal structures of MuV-HN proteins bound to newly identified glycan motifs, sialyl Lewis X (SLe X ) and the oligosaccharide portion of the GM2 ganglioside (GM2-glycan). Interestingly, the complex structures showed that SLe X and GM2-glycan share the same configuration with the reported trisaccharide motif, 3'-sialyllactose (3'-SL), at the binding site of MuV-HN, while SLe X and GM2-glycan have several unique interactions compared with those of 3'-SL. Thus, MuV-HN protein can allow an additional spatial modification in GM2-glycan and SLe X at the second and third carbohydrates from the nonreducing terminus of the core trisaccharide structure, respectively. Importantly, MuV entry was efficiently inhibited in the presence of 3'-SL, SLe X , or GM2-glycan derivatives, which indicates that these motifs can serve as MuV receptors. The α2,3-sialylated oligosaccharides, such as SLe X and 3'-sialyllactosamine, are broadly expressed in various tissues, and GM2 exists mainly in neural tissues and the adrenal gland. The distribution of these glycan motifs in human tissues/organs may have bearing on MuV tropism. IMPORTANCE Mumps virus (MuV) infection is characterized by parotid gland swelling and can cause pancreatitis, orchitis, meningitis, and encephalitis. MuV-related hearing loss is also a serious complication because it is usually irreversible. MuV outbreaks have been reported in many countries, even in high-vaccine-coverage areas. MuV has tropism toward glandular tissues and the central nervous system. To understand the unique MuV tropism, revealing the mechanism of receptor recognition by MuV is very important. Here, using a large-scale glycan array and X-ray crystallography, we show that MuV recognizes sialyl Lewis X and GM2 ganglioside as receptors, in addition to a previously reported MuV receptor, a trisaccharide containing an α2,3-linked sialic acid. The flexible recognition of these glycan receptors by MuV may explain the unique tropism and pathogenesis of MuV. Structures will also provide a template for the development of effective entry inhibitors targeting the receptor-binding site of MuV.


  • Organizational Affiliation

    Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
HN protein
A, B
489Mumps orthorubulavirusMutation(s): 0 
Gene Names: HN
UniProt
Find proteins for Q9WAF5 (Mumps orthorubulavirus)
Explore Q9WAF5 
Go to UniProtKB:  Q9WAF5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9WAF5
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C, D, F, G
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
N-acetyl-alpha-neuraminic acid-(2-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]beta-D-galactopyranose-(1-4)-beta-D-glucopyranose
E, H
4N/A
Glycosylation Resources
GlyTouCan:  G28331VY
GlyCosmos:  G28331VY
GlyGen:  G28331VY
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.184 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 137.257α = 90
b = 137.257β = 90
c = 178.009γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data collection
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Japan Agency for Medical Research and Development (AMED)JapanJP18fk0108014h
Ministry of Education, Culture, Sports, Science and Technology (Japan)Japan24115005
Ministry of Education, Culture, Sports, Science and Technology (Japan)Japan17H05820

Revision History  (Full details and data files)

  • Version 1.0: 2019-05-22
    Type: Initial release
  • Version 1.1: 2019-06-12
    Changes: Data collection, Database references
  • Version 1.2: 2019-07-31
    Changes: Data collection, Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary