HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 1, 593-602, January 4, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/1/593    most recent M706292200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Powlesland, A. S. Articles by Drickamer, K. Search for Related Content PubMed PubMed Citation Articles by Powlesland, A. S. Articles by Drickamer, K. Social Bookmarking                      What's this?

A Novel Mechanism for LSECtin Binding to Ebola Virus Surface Glycoprotein through Truncated Glycans^*

Alex S. Powlesland, Tanja Fisch, Maureen E. Taylor, David F. Smith^¶, Bérangère Tissot¹, Anne Dell², Stefan Pöhlmann^||, and Kurt Drickamer³

From the Division of Molecular Biosciences, Imperial College, London SW7 2AZ, United Kingdom, Institute of Virology and Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nürnberg, 91054 Erlangen, Germany, ^||Institute of Virology, Hannover Medical School, 30625 Hannover, Germany, and ^¶Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322

LSECtin is a member of the C-type lectin family of glycan-binding receptors that is expressed on sinusoidal endothelial cells of the liver and lymph nodes. To compare the sugar and pathogen binding properties of LSECtin with those of related but more extensively characterized receptors, such as DC-SIGN, a soluble fragment of LSECtin consisting of the C-terminal carbohydrate-recognition domain has been expressed in bacteria. A biotin-tagged version of the protein was also generated and complexed with streptavidin to create tetramers. These forms of the carbohydrate-recognition domain were used to probe a glycan array and to characterize binding to oligosaccharide and glycoprotein ligands. LSECtin binds with high selectivity to glycoproteins terminating in GlcNAcβ1-2Man. The inhibition constant for this disaccharide is 3.5 µM, making it one of the best low molecular weight ligands known for any C-type lectin. As a result of the selective binding of this disaccharide unit, the receptor recognizes glycoproteins with a truncated complex and hybrid N-linked glycans on glycoproteins. Glycan analysis of the surface glycoprotein of Ebola virus reveals the presence of such truncated glycans, explaining the ability of LSECtin to facilitate infection by Ebola virus. High mannose glycans are also present on the viral glycoprotein, which explains why DC-SIGN also binds to this virus. Thus, multiple receptors interact with surface glycoproteins of enveloped viruses that bear different types of relatively poorly processed glycans.

Received for publication, July 31, 2007 , and in revised form, October 9, 2007.

^* This work was supported in part by Wellcome Trust Grant 041845 (to K. D. and M. E. T.), a grant from the Biotechnology and Biological Sciences Research Council (to A. D.), Deutsche Forschungsgemeinschaft Grant SFB466 (to T. F. and S. P.), and NIGMS, National Institutes of Health Grant GM62116 (to the Consortium for Functional Glycomics). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1.

¹ Funded by the Research Councils United Kingdom Basic Technology Programme (UK GlycoArrays Consortium grant).

² A Biotechnology and Biological Sciences Research Council Professorial Research Fellow.

³ To whom correspondence should be addressed: Division of Molecular Biosciences, Biochemistry Bldg., Imperial College, London SW7 2AZ, UK. Tel.: 44-20-7594-5282; Fax: 44-20-7594-3057; E-mail: k.drickamer{at}imperial.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Dube, M. B. Brecher, S. E. Delos, S. C. Rose, E. W. Park, K. L. Schornberg, J. H. Kuhn, and J. M. White The Primed Ebolavirus Glycoprotein (19-Kilodalton GP1,2): Sequence and Residues Critical for Host Cell Binding J. Virol., April 1, 2009; 83(7): 2883 - 2891. [Abstract] [Full Text] [PDF]

				T. A. Bowden, M. Crispin, D. J. Harvey, A. R. Aricescu, J. M. Grimes, E. Y. Jones, and D. I. Stuart Crystal Structure and Carbohydrate Analysis of Nipah Virus Attachment Glycoprotein: a Template for Antiviral and Vaccine Design J. Virol., December 1, 2008; 82(23): 11628 - 11636. [Abstract] [Full Text] [PDF]