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Journal of Virology, December 2002, p. 13028-13033, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.13028-13033.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Role of the Hemagglutinin-Neuraminidase Protein in the Mechanism of Paramyxovirus-Cell Membrane Fusion

Toru Takimoto,1* Garry L. Taylor,2 Helen C. Connaris,2 Susan J. Crennell,3 and Allen Portner1

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,1 Centre for Biomolecular Sciences, The University of St. Andrews, St. Andrews, Fife KY16 9ST, Scotland,2 Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom3

Received 24 May 2002/ Accepted 4 September 2002

Paramyxovirus infects cells by initially attaching to a sialic acid-containing cellular receptor and subsequently fusing with the plasma membrane of the cells. Hemagglutinin-neuraminidase (HN) protein, which is responsible for virus attachment, interacts with the fusion protein in a virus type-specific manner to induce efficient membrane fusion. To elucidate the mechanism of HN-promoted membrane fusion, we characterized a series of Newcastle disease virus HN proteins whose surface residues were mutated. Fusion promotion activity was substantially altered in only the HN proteins with a mutation in the first or sixth ß sheet. These regions overlap the large hydrophobic surface of HN; thus, the hydrophobic surface may contain the fusion promotion domain. Furthermore, a comparison of the HN structure crystallized alone or in complex with 2-deoxy-2,3-dehydro-N-acetylneuraminic acid revealed substantial conformational changes in several loops within or near the hydrophobic surface. Our results suggest that the binding of HN protein to the receptor induces the conformational change of residues near the hydrophobic surface of HN protein and that this change triggers the activation of the F protein, which initiates membrane fusion.

* Corresponding author. Mailing address: Department of Infectious Diseases, Mail Stop 330, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794. Phone: (901) 495-3375. Fax: (901) 523-2622. E-mail: toru.takimoto{at}stjude.org.

Journal of Virology, December 2002, p. 13028-13033, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.13028-13033.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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