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Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4

Nature Structural & Molecular Biology volume 20, pages 67–72 (2013)Cite this article

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Abstract

Measles virus is a major public health concern worldwide. Three measles virus cell receptors have been identified so far, and the structures of the first two in complex with measles virus hemagglutinin (MV-H) have been reported. Nectin-4 is the most recently identified receptor in epithelial cells, and its binding mode to MV-H remains elusive. In this study, we solved the structure of the membrane-distal domain of human nectin-4 in complex with MV-H. The structure shows that nectin-4 binds the MV-H β4-β5 groove exclusively via its N-terminal IgV domain; the contact interface is dominated by hydrophobic interactions. The binding site in MV-H for nectin-4 also overlaps extensively with those of the other two receptors. Finally, a hydrophobic pocket centered in the β4-β5 groove is involved in binding to all three identified measles virus receptors, representing a potential target for antiviral drugs.

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Figure 1: Nectin-4 binds to the β4-β5 groove of MV-H via its N-terminal IgV domain.
Figure 2: Dimeric organization of the MV-H–nectin-4v complex.
Figure 3: Binding interface between MV-H (green) and nectin-4v (purple).
Figure 4: Comparison of MV-H binding to its three receptors.

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Acknowledgements

This work was supported by the 973 Project of the China Ministry of Science and Technology (MOST, grants 2011CB504703 and 2010CB911902, G.F.G.). We acknowledge assistance by the staff at the Shanghai Synchrotron Radiation Facility of China. We thank Y. Zhang, X. Yu and T. Zhao for their expert technical assistance. G.F.G. is a leading principal investigator of the Innovative Research Group of the National Natural Science Foundation of China (grant 81021003).

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Author notes

  1. Xiaoai Zhang and Guangwen Lu: These authors contributed equally to this work.

Authors and Affiliations

  1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China

    Xiaoai Zhang, Guangwen Lu, Jianxun Qi, Yan Li, Jinghua Yan & George F Gao

  2. Beijing QuantoBio Biotechnology Co. Ltd., Beijing, China

    Yan He, Jia Shi & Catherine W-H Zhang

  3. College of Life Science, Anhui Agricultural University, Hefei, China

    Xiang Xu

  4. Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.,

    George F Gao

  5. Chinese Center for Disease Control and Prevention, Changping District, Beijing, China

    George F Gao

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  1. Xiaoai Zhang
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Contributions

G.F.G. conceived, designed and supervised the project. X.Z., G.L., X.X., Y.L., Y.H., J.S. and C.W.-H.Z. did the experiments. J.Q. collected the data and solved the structure. G.L., J.Y. and G.F.G. analyzed the data and wrote the paper.

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Correspondence to George F Gao.

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Zhang, X., Lu, G., Qi, J. et al. Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4. Nat Struct Mol Biol 20, 67–72 (2013). https://doi.org/10.1038/nsmb.2432

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