DOI: 10.1126/science.1066371. Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR

Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR

10.1126/science.1066371

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Dendritic cell specific intracellular adhesion molecule–3 (ICAM-3) grabbing nonintegrin (DC-SIGN), a C-type lectin present on the surface of dendritic cells, mediates the initial interaction of dendritic cells with T cells by binding to ICAM-3. DC-SIGN and DC-SIGNR, a related receptor found on the endothelium of liver sinusoids, placental capillaries, and lymph nodes, bind to oligosaccharides that are present on the envelope of human immunodeficiency virus (HIV), an interaction that strongly promotes viral infection of T cells. Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR bound to oligosaccharide, in combination with binding studies, reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides and may represent a new avenue for developing HIV prophylactics.

Bibliography

Feinberg, H., Mitchell, D. A., Drickamer, K., & Weis, W. I. (2001). Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR. Science, 294(5549), 2163â2166.

Authors 4

Hadar Feinberg (first)
Daniel A. Mitchell (additional)
Kurt Drickamer (additional)
William I. Weis (additional)

References 22 Referenced 597

10.1038/32588
Geijtenbeek T. B. H., et al., Cell 100, 575 (2000). (10.1016/S0092-8674(00)80693-5) / Cell by Geijtenbeek T. B. H. (2000)
Geijtenbeek T. B. H., et al., Nature Immunol. 1, 353 (2000). (10.1038/79815) / Nature Immunol. by Geijtenbeek T. B. H. (2000)
Mitchell D. A., Fadden A. J., Drickamer K., J. Biol. Chem. 276, 28939 (2001). (10.1074/jbc.M104565200) / J. Biol. Chem. by Mitchell D. A. (2001)
Weis W. I., Taylor M. E., Drickamer K., Immunol. Rev. 163, 19 (1998). (10.1111/j.1600-065X.1998.tb01185.x) / Immunol. Rev. by Weis W. I. (1998)
Soilleux E. J., Barten R., Trowsdale J., J. Immunol. 165, 2937 (2000). (10.4049/jimmunol.165.6.2937) / J. Immunol. by Soilleux E. J. (2000)
Pöhlmann S., et al., Proc. Natl. Acad. Sci. U.S.A. 98, 2670 (2001). (10.1073/pnas.051631398) / Proc. Natl. Acad. Sci. U.S.A. by Pöhlmann S. (2001)
Bashirova A. A., et al., J. Exp. Med. 193, 671 (2001). (10.1084/jem.193.6.671) / J. Exp. Med. by Bashirova A. A. (2001)
10.1016/S0092-8674(00)80694-7
Pöhlmann S., et al., J. Virol. 75, 4664 (2001). (10.1128/JVI.75.10.4664-4672.2001) / J. Virol. by Pöhlmann S. (2001)
Supplemental data are available on Science Online at www.sciencemag.org/cgi/content/full/294/5549/2163/DC1.
Drickamer K., Curr. Opin. Struct. Biol. 9, 585 (1999). (10.1016/S0959-440X(99)00009-3) / Curr. Opin. Struct. Biol. by Drickamer K. (1999)
Petrescu A. J., Petrescu S. M., Dwek R. A., Wormald M. R., Glycobiology 9, 343 (1999). (10.1093/glycob/9.4.343) / Glycobiology by Petrescu A. J. (1999)
Mizuochi T., et al., J. Biol. Chem. 265, 8519 (1990). (10.1016/S0021-9258(19)38919-7) / J. Biol. Chem. by Mizuochi T. (1990)
Woods R. J., Pathiaseril A., Wormald M. R., Edge C. J., Dwek R. A., Eur. J. Biochem. 258, 372 (1998). (10.1046/j.1432-1327.1998.2580372.x) / Eur. J. Biochem. by Woods R. J. (1998)
The weak interaction with a GlcNAc-terminated neoglycolipid derived from an asialo aglacto-bantennary N-linked glycan can be explained by the interaction of a terminal GlcNAc residue with the principal Ca 2+ site as observed in the cross-linked pairs of CRDs of DC-SIGN (Fig. 3B). This interpretation is confirmed by the observation that the corresponding galactose-terminated structure in which the 4-OH of GlcNAc is inaccessible does not bind at all. Moreover modeling of a further mannose residue in α1-2 linkage to the Manα1-3Man arm of the trimannosyl moiety suggests that it would pack against Val 351 of DC-SIGN whereas no contact would be made with the smaller Ser 363 present at this position of DC-SIGNR. This observation may be related to the larger affinity difference between Man 9 and smaller oligosaccharides displayed by DC-SIGN relative to DC-SIGNR [see (4) and table 2 of supplemental data (11)].
Weis W. I., Drickamer K., Hendrickson W. A., Nature 360, 127 (1992). (10.1038/360127a0) / Nature by Weis W. I. (1992)
Weis W. I., Drickamer K., Structure 2, 1227 (1994). (10.1016/S0969-2126(94)00124-3) / Structure by Weis W. I. (1994)
A. Nicholls GRASP: Graphical Representation and Analysis of Surface Properties (Columbia University New York 1992).
10.1016/S0076-6879(97)76066-X
10.1107/S0021889892009944
We thank E. Soilleux for providing cDNAs; D. Torgersen for assistance with protein preparation; G. Golan O. Livnah and G. Shoham of the Hebrew University for assistance with data collection; and L. Tong for the COMO program. Some of this work is based upon research conducted at the Stanford Synchrotron Radiation Laboratory (SSRL) a national facility operated by Stanford University for the DOE Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program is supported by the Department of Energy Office of Biological and Environmental Research and by the National Center for Research Resources Biomedical Technology Program and National Institute of General Medical Sciences NIH. Part of this research was carried out at the National Synchrotron Light Source Brookhaven National Laboratory which is supported by the DOE Division of Materials Sciences and Division of Chemical Sciences. Supported by grants 041845 and 054508 from the Wellcome Trust (K.D.) and grant GM50565 from the NIH (W.I.W.). Coordinates and structure factors have been deposited in the Protein Data Bank with accession codes 1K9I (DC-SIGN) and 1K9J (DC-SIGNR).

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:47 a.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 5:31 p.m.)
Indexed	3 days, 14 hours ago (Aug. 30, 2025, 12:51 p.m.)
Issued	23 years, 8 months ago (Dec. 7, 2001)
Published	23 years, 8 months ago (Dec. 7, 2001)
Published Print	23 years, 8 months ago (Dec. 7, 2001)

Funders 0

None

BibTeX

@article{Feinberg_2001, title={Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR}, volume={294}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1066371}, DOI={10.1126/science.1066371}, number={5549}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Feinberg, Hadar and Mitchell, Daniel A. and Drickamer, Kurt and Weis, William I.}, year={2001}, month=dec, pages={2163–2166} }

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