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

Abstract

Measles virus, a major cause of childhood morbidity and mortality worldwide, predominantly infects immune cells using signaling lymphocyte activation molecule (SLAM) as a cellular receptor. Here we present crystal structures of measles virus hemagglutinin (MV-H), the receptor-binding glycoprotein, in complex with SLAM. The MV-H head domain binds to a β-sheet of the membrane-distal ectodomain of SLAM using the side of its β-propeller fold. This is distinct from attachment proteins of other paramyxoviruses that bind receptors using the top of their β-propeller. The structure provides templates for antiviral drug design, an explanation for the effectiveness of the measles virus vaccine, and a model of the homophilic SLAM-SLAM interaction involved in immune modulations. Notably, the crystal structures obtained show two forms of the MV-H–SLAM tetrameric assembly (dimer of dimers), which may have implications for the mechanism of fusion triggering.

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Figure 1: Overall structure of the MV-H–SLAM complex.
Figure 2: Interaction between MV-H and SLAM.
Figure 3: MV-H tetramer.
Figure 4: Structural basis of effectiveness of measles virus vaccine and a model of measles virus–induced membrane fusion.

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NCBI Reference Sequence

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Acknowledgements

We thank the beamline staff of Photon Factory (Tsukuba, Japan) and SPring8 (Hyogo, Japan) for technical help during data collection. We also thank M.A. Billeter (Institute of Molecular Biology, University of Zürich) for reagents, M. Takeda, I. Tanaka, K. Inaba, K. Mihara, T. Oka, H. Aramaki, K. Tokunaga, M. Kajikawa, K. Kuroki and K. Sasaki for discussion and E.O. Saphire for reviewing the manuscript. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health, Labor and Welfare of Japan. T.H. is supported by the Japan Society for the Promotion of Science Research Fellowship for Young Scientists.

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T.H., K.M. and Y.Y. designed the research; T.H. and J.K. prepared and crystallized MV-H–SLAM complexes; T.H. and M.K. carried out binding, BN-PAGE and measles virus infection assays; T.H., T.O., N.M. and K.M. determined the crystal structures; T.H., K.M. and Y.Y. wrote the paper.

Corresponding authors

Correspondence to Katsumi Maenaka or Yusuke Yanagi.

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Hashiguchi, T., Ose, T., Kubota, M. et al. Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM. Nat Struct Mol Biol 18, 135–141 (2011). https://doi.org/10.1038/nsmb.1969

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