Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM

Hanabusa, Takao; Ose, Toyoyuki; Kubota, Mitsuru; Maita, N.; Kamishikiryo, Jun; Maenaka, Katsumi; Yanagi, Yusuke

doi:10.1038/nsmb.1969

Cited by 230 publications

(436 citation statements)

References 46 publications

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“…Other important HN-F interactions or conformational changes, such as rearrangements of the NA domains, could also play a role in F activation (6). For measles virus H, functional and structural evidence for such domain rearrangements has been reported (28,29). For NDV HN, disulfide bond cross-linking between NA1/NA2 and NA3/NA4 dimers enhances membrane fusion (30), but dimer of dimer arrangements and NA to stalk domain interactions might contribute to fusion activation.…”

Section: Discussionmentioning

confidence: 99%

Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk

Yuan

Swanson

Leser

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

156

266

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The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles in viral entry and egress, including binding to sialic acid receptors, activating the fusion (F) protein to activate membrane fusion and viral entry, and cleaving sialic acid from carbohydrate chains. HN is an oligomeric integral membrane protein consisting of an N-terminal transmembrane domain, a stalk region, and an enzymatically active neuraminidase (NA) domain. Structures of the HN NA domains have been solved previously; however, the structure of the stalk region has remained elusive. The stalk region contains specificity determinants for F interactions and activation, underlying the requirement for homotypic F and HN interactions in viral entry. Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F activation and NA activities, but a structural basis for understanding these dual affects on HN functions has been lacking. Here, we report the structure of the Newcastle disease virus HN ectodomain, revealing dimers of NA domain dimers flanking the N-terminal stalk domain. The stalk forms a parallel tetrameric coiled-coil bundle (4HB) that allows classification of extensive mutational data, providing insight into the functional roles of the stalk region. Mutations that affect both F activation and NA activities map predominantly to the 4HB hydrophobic core, whereas mutations that affect only F-protein activation map primarily to the 4HB surface. Two of four NA domains interact with the 4HB stalk, and residues at this interface in both the stalk and NA domain have been implicated in HN function.

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Section: Discussionmentioning

confidence: 99%

Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk

Yuan

Swanson

Leser

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

156

266

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“…Interestingly, the similarly positioned α-helix is known as the hemagglutinin noose epitope (HNE; residues at positions 379-410) in measles virus H (28). Given that these epitopes on α-helices (helices A, B, and C on MuV-NH and HNE on measles virus H) apparently are not involved in receptor binding (15,29), Abs against them are likely to neutralize the viruses by mechanisms other than the inhibition of receptor binding. Whereas amino acid residues in the HNE region of measles virus H are highly conserved (28), those of the MuV-HN α-helices exhibit diversity among the different genotypes of MuV (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…NCI-H358 cells were maintained in RPMI medium (Wako) supplemented with 10% (vol/vol) FBS and penicillin/streptomycin. The expression, purification, crystallization, and structure determination of proteins were carried out as described previously (15,29), with some modifications. The MD simulation was performed with Gromacs 5.0.5 (30).…”

Section: Methodsmentioning

confidence: 99%

Trisaccharide containing α2,3-linked sialic acid is a receptor for mumps virus

Kubota

Takeuchi

Watanabe

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mumps virus (MuV) remains an important pathogen worldwide, causing epidemic parotitis, orchitis, meningitis, and encephalitis. Here we show that MuV preferentially uses a trisaccharide containing α2,3-linked sialic acid in unbranched sugar chains as a receptor. Crystal structures of the MuV attachment protein hemagglutinin-neuraminidase (MuV-HN) alone and in complex with the α2,3-sialylated trisaccharide revealed that in addition to the interaction between the MuV-HN active site residues and sialic acid, other residues, including an aromatic residue, stabilize the third sugar of the trisaccharide. The importance of the aromatic residue and the third sugar in the MuV-HN−receptor interaction was confirmed by computational energy calculations, isothermal titration calorimetry studies, and glycan-binding assays. Furthermore, MuV-HN was found to bind more efficiently to unbranched α2,3-sialylated sugar chains compared with branched ones. Importantly, the strategically located aromatic residue is conserved among the HN proteins of sialic acid-using paramyxoviruses, and alanine substitution compromised their ability to support cellcell fusion. These results suggest that not only the terminal sialic acid but also the adjacent sugar moiety contribute to receptor function for mumps and these paramyxoviruses. The distribution of structurally different sialylated glycans in tissues and organs may explain in part MuV's distinct tropism to glandular tissues and the central nervous system. In the crystal structure, the epitopes for neutralizing antibodies are located around the α-helices of MuV-HN that are not well conserved in amino acid sequences among different genotypes of MuV. This may explain the fact that MuV reinfection sometimes occurs. structure | entry | receptor | infection | paramyxovirus

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“…Future research should therefore focus on insuring against such an eventuality. One option is to concentrate analysis on the ectodomain region of the H ORF, as is the case for MeV [73], since these data can also be translated into functional information on receptor binding [74] or antigenicity [75], while still providing sufficient data to cluster the viruses phylogenetically along similar lines to the existing N-and F-based systems (Fig. 3).…”

Section: Novel Tools In the Pipelinementioning

confidence: 99%

Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

Baron

Diop

Njeumi

et al. 2017

Journal of General Virology

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Peste des petits ruminants virus (PPRV) is a significant pathogen of small ruminants and is prevalent in much of Africa, the Near and Middle East and Asia. Despite the availability of an efficacious and cheap live-attenuated vaccine, the virus has continued to spread, with its range stretching from Morocco in the west to China and Mongolia in the east. Some of the world's poorest communities rely on small ruminant farming for subsistence and the continued endemicity of PPRV is a constant threat to their livelihoods. Moreover, PPRV's effects on the world's population are felt broadly across many economic, agricultural and social situations. This far-reaching impact has prompted the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) to develop a global strategy for the eradication of this virus and its disease. PPRV is a morbillivirus and, given the experience of these organizations in eradicating the related rinderpest virus, the eradication of PPRV should be feasible. However, there are many critical areas where basic and applied virological research concerning PPRV is lacking. The purpose of this review is to highlight areas where new research could be performed in order to guide and facilitate the eradication programme. These areas include studies on disease transmission and epidemiology, the existence of wildlife reservoirs and the development of next-generation vaccines and diagnostics. With the support of the international virology community, the successful eradication of PPRV can be achieved.

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Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM

Cited by 230 publications

References 46 publications

Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk

Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk

Trisaccharide containing α2,3-linked sialic acid is a receptor for mumps virus

Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

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