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Structure of the measles virus hemagglutinin bound to the CD46 receptor

Nature Structural & Molecular Biology volume 17, pages 124129 (2010) | Download Citation

Abstract

The highly contagious measles virus infects millions of individuals worldwide, causing serious disease in children of developing countries. Infection is initiated by attachment of the measles virus hemagglutinin (MV-H), a glycoprotein anchored to the virus envelope, to the host cell receptors CD46 or signaling lymphocyte activation molecule (SLAM). Here we report the crystal structure of MV-H in complex with a CD46 protein spanning the two N-terminal domains. A unique groove at the side of the MV-H β-propeller domain, which is absent in homologous paramyxovirus attachment proteins, engages residues in both CD46 domains. Key contacts involve a protruding loop in the N-terminal CD46 domain that carries two sequential proline residues (PP motif) and penetrates deeply into a hydrophobic socket in MV-H. We identify a similar PP motif in SLAM, defining a common measles virus recognition epitope in the CD46 and SLAM receptor proteins.

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Acknowledgements

We are grateful to F. Pazos for assistance with secondary structure prediction and to R. Fernandez-Muñoz for helpful discussions. We acknowledge the European Molecular Biology Laboratory, the Deutsches Elektronen Synchrotron and the European Synchrotron Radiation Facility for provision of synchrotron radiation facilities. This work has been supported by grants from the Ministerio de Ciencia e Innovación (BFU2005-05972 and BFU2008-00971) to J.M.C. T.S. acknowledges support from SFB-685.

Author information

Affiliations

  1. Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Campus Universidad Autónoma, Madrid, Spain.

    • César Santiago
    •  & José M Casasnovas
  2. Virology Unit, Hospital Ramón y Cajal, Madrid, Spain.

    • María L Celma
  3. Interfaculty Institute for Biochemistry, University of Tuebingen, Tuebingen, Germany.

    • Thilo Stehle
  4. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Thilo Stehle

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Contributions

C.S. and J.M.C. designed the constructs. C.S. prepared the proteins and crystallized the MV-H–CD46 complex. C.S. and J.M.C. contributed to data collection and structure determination. C.S., T.S. and J.M.C. performed structure refinement and model building. C.S., M.L.C., T.S. and J.M.C. contributed to analysis of the data and preparation of the manuscript.

Corresponding author

Correspondence to José M Casasnovas.

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DOI

https://doi.org/10.1038/nsmb.1726

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