6jjm

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

spinqualitylabelsall models 6jjm, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6jjm is a 2 chain structure with sequence from Mumps orthorubulavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.049Å Ligands: BGC, GAL, NAG, SIA, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9WAF5_9MONO Publication Abstract from PubMed Mumps virus (MuV) is an important aerosol-transmitted human pathogen causing epidemic parotitis, meningitis, encephalitis, and deafness. MuV preferentially uses a trisaccharide containing alpha2,3-linked sialic acid as a receptor. However, considering MuV tropism toward glandular tissues and the central nervous system, additional glycan motif(s) may also serve as receptors. 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 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 3'-SL. Thus, MuV-HN protein can allow an additional spatial modification in GM2-glycan and SLe(X) at the second and third carbohydrate 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 alpha2,3-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.ImportanceMumps 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 alpha2,3-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. Molecular mechanism of the flexible glycan-receptor recognition by mumps virus.,Kubota M, Matsuoka R, Suzuki T, Yonekura K, Yanagi Y, Hashiguchi T J Virol. 2019 May 22. pii: JVI.00344-19. doi: 10.1128/JVI.00344-19. PMID:31118251 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Hemagglutinin 3D structures

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