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

J. Biol. Chem., Vol. 279, Issue 18, 19122-19132, April 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/18/19122    most recent M400184200v1 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 Su, S. V. Articles by Lee, B. Search for Related Content PubMed PubMed Citation Articles by Su, S. V. Articles by Lee, B. Social Bookmarking                      What's this?

DC-SIGN Binds to HIV-1 Glycoprotein 120 in a Distinct but Overlapping Fashion Compared with ICAM-2 and ICAM-3^*

Stephen V. Su, Patrick Hong, Sarah Baik, Oscar A. Negrete, Kevin B. Gurney, and Benhur Lee¶||

From the Department of Microbiology, Immunology, and Molecular Genetics, the Department of Pathology and Laboratory Medicine, ^¶UCLA AIDS Institute, David Geffen School of Medicine, UCLA, Los Angeles, California 90095

DC-SIGN is a C-type lectin that binds to endogenous adhesion molecules ICAM-2 and ICAM-3 as well as the viral envelope glycoprotein human immunodeficiency virus, type 1, glycoprotein (gp) 120. We wished to determine whether DC-SIGN binds differently to its endogenous ligands ICAM-2 and ICAM-3 versus HIV-1 gp120. We found that recombinant soluble DC-SIGN bound to gp120-Fc more than 100- and 50-fold better than ICAM-2-Fc and ICAM-3-Fc, respectively. This relative difference was maintained using DC-SIGN expressed on three different CD4-negative cell lines. Although the cell surface affinity for gp120 varied by up to 4-fold on the cell lines examined, the affinity for gp120 was not a correlate of the ability of the cell line to transfer virus. Monosaccharides with equatorial 4-OH groups competed as well as D-mannose for gp120 binding to DC-SIGN, regardless of how the other hydroxyl groups were positioned. Disaccharide competitors and glycan chip analysis showed that DC-SIGN has a preference for oligosaccharides linked in an -anomeric configuration. Alanine-scanning mutagenesis of DC-SIGN revealed that highly conserved residues that coordinate calcium (Asp-366) and/or are involved in both calcium and specific carbohydrate interactions (Glu-347, Asn-349, Glu-354, and Asp-355) significantly compromised binding to all three ligands. Mutating non-conserved residues (Asn-311, Arg-345, Val-351, Gly-352, Glu-353, Ser-360, Gly-361, and Asn-362) minimally affected binding except for the Asp-367 mutant, which enhanced gp120 binding but diminished ICAM-2 and ICAM-3 binding. Conversely, mutating the moderately conserved residue (Gly-346) abrogated gp120 binding but enhanced ICAM-2 and ICAM-3 binding. Thus, DC-SIGN appears to bind in a distinct but overlapping manner to gp120 when compared with ICAM-2 and ICAM-3.

Received for publication, January 8, 2004 , and in revised form, February 7, 2004.

^* This work was supported in part by the UCLA AIDS Institute, flow cytometry core UCLA CFAR Grant AI-28697 from the National Institutes of Health, and the James B. Pendleton Charitable Trust. 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.

^|| Charles E. Culpepper Medical Scholar supported by the Rockefeller Brothers Fund, a recipient of the Burroughs Wellcome Fund career development award, and National Institutes of Health Grants RO1-AI52021 and R21-AI055305. To whom correspondence should be addressed: Dept. of Microbiology, Immunology, and Molecular Genetics, 3821 Molecular Sciences Bldg., 609 Charles E. Young Dr. East, Los Angeles, CA 90095. Tel.: 310-794-2132; Fax: 310-267-2580; E-mail: benhurL{at}microbio.ucla.edu.

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

This article has been cited by other articles:

				R. J. Luallen, H. Fu, C. Agrawal-Gamse, I. Mboudjeka, W. Huang, F.-H. Lee, L.-X. Wang, R. W. Doms, and Y. Geng A Yeast Glycoprotein Shows High-Affinity Binding to the Broadly Neutralizing Human Immunodeficiency Virus Antibody 2G12 and Inhibits gp120 Interactions with 2G12 and DC-SIGN J. Virol., May 15, 2009; 83(10): 4861 - 4870. [Abstract] [Full Text] [PDF]

				J.-H. Wang, C. Kwas, and L. Wu Intercellular Adhesion Molecule 1 (ICAM-1), but Not ICAM-2 and -3, Is Important for Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission J. Virol., May 1, 2009; 83(9): 4195 - 4204. [Abstract] [Full Text] [PDF]

				D. Serrano-Gomez, E. Sierra-Filardi, R. T. Martinez-Nunez, E. Caparros, R. Delgado, M. A. Munoz-Fernandez, M. A. Abad, J. Jimenez-Barbero, M. Leal, and A. L. Corbi Structural Requirements for Multimerization of the Pathogen Receptor Dendritic Cell-specific ICAM3-grabbing Non-integrin (CD209) on the Cell Surface J. Biol. Chem., February 15, 2008; 283(7): 3889 - 3903. [Abstract] [Full Text] [PDF]

				P. W.-P. Hong, S. Nguyen, S. Young, S. V. Su, and B. Lee Identification of the Optimal DC-SIGN Binding Site on Human Immunodeficiency Virus Type 1 gp120 J. Virol., August 1, 2007; 81(15): 8325 - 8336. [Abstract] [Full Text] [PDF]

				N. M. Moutsopoulos, S. Nares, N. Nikitakis, Z. Rangel, J. Wen, P. Munson, J. Sauk, and S. M. Wahl Tonsil Epithelial Factors May Influence Oropharyngeal Human Immunodeficiency Virus Transmission Am. J. Pathol., August 1, 2007; 171(2): 571 - 579. [Abstract] [Full Text] [PDF]

				N. Dakappagari, T. Maruyama, M. Renshaw, P. Tacken, C. Figdor, R. Torensma, M. A. Wild, D. Wu, K. Bowdish, and A. Kretz-Rommel Internalizing Antibodies to the C-Type Lectins, L-SIGN and DC-SIGN, Inhibit Viral Glycoprotein Binding and Deliver Antigen to Human Dendritic Cells for the Induction of T Cell Responses J. Immunol., January 1, 2006; 176(1): 426 - 440. [Abstract] [Full Text] [PDF]

				H. Feinberg, Y. Guo, D. A. Mitchell, K. Drickamer, and W. I. Weis Extended Neck Regions Stabilize Tetramers of the Receptors DC-SIGN and DC-SIGNR J. Biol. Chem., January 14, 2005; 280(2): 1327 - 1335. [Abstract] [Full Text] [PDF]

				E. Van Liempt, A. Imberty, C. M. C. Bank, S. J. Van Vliet, Y. Van Kooyk, T. B. H. Geijtenbeek, and I. Van Die Molecular Basis of the Differences in Binding Properties of the Highly Related C-type Lectins DC-SIGN and L-SIGN to Lewis X Trisaccharide and Schistosoma mansoni Egg Antigens J. Biol. Chem., August 6, 2004; 279(32): 33161 - 33167. [Abstract] [Full Text] [PDF]