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

J. Biol. Chem., Vol. 281, Issue 52, 40369-40378, December 29, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/52/40369    most recent M608518200v1 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 Paduraru, C. Articles by Cresswell, P. Search for Related Content PubMed PubMed Citation Articles by Paduraru, C. Articles by Cresswell, P. Social Bookmarking                      What's this?

An N-Linked Glycan Modulates the Interaction between the CD1d Heavy Chain and ₂-Microglobulin^*

Crina Paduraru, Laurentiu Spiridon, Weiming Yuan¹, Gabriel Bricard^¶, Xavier Valencia^¶, Steven A. Porcelli^¶2, Petr A. Illarionov^||, Gurdyal S. Besra^||3, Stefana M. Petrescu, Andrei-Jose Petrescu, and Peter Cresswell⁴

From the Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, the Institute of Biochemistry, Splaiul Independentei 296, 060031 Bucharest 17, Romania, the ^¶Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, and the ^||Department of Microbial Physiology and Chemistry, School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom

Human CD1d molecules consist of a transmembrane CD1 (cluster of differentiation 1) heavy chain in association with ₂-microglobulin (₂m). Assembly occurs in the endoplasmic reticulum (ER) and involves the initial glycan-dependent association of the free heavy chain with calreticulin and calnexin and the thiol oxidoreductase ERp57. Folding and disulfide bond formation within the heavy chain occurs prior to ₂m binding. There are four N-linked glycans on the CD1d heavy chain, and we mutated them individually to ascertain their importance for the assembly and function of CD1d-₂m heterodimers. None of the four were indispensable for assembly or the ability to bind -galactosyl ceramide and to present it to human NKT cells. Nor were any required for the CD1d molecule to bind and present -galactosyl ceramide after lysosomal processing of a precursor lipid, galactosyl-(1-2)-galactosyl ceramide. However, one glycan, glycan 2 at Asn-42, proved to be of particular importance for the stability of the CD1d-₂m heterodimer. A mutant CD1d heavy chain lacking glycan 2 assembled with ₂m and transported from the ER more rapidly than wild-type CD1d and dissociated more readily from ₂m upon exposure to detergents. A mutant expressing only glycan 1 dissociated completely from ₂m upon exposure to the detergent Triton X-100, whereas a mutant expressing only glycan 2 at Asn-42 was more stable. In addition, glycan 2 was not processed efficiently to the complex form in mature wild-type CD1d molecules. Modeling the glycans on the published structure indicated that glycan 2 interacts significantly with both the CD1d heavy chain and ₂m, which may explain these unusual properties.

Received for publication, September 5, 2006 , and in revised form, October 26, 2006.

^* This work was supported in part by a grant from the Howard Hughes Medical Institute and National Institutes of Health Grant AI059167 (to P. C.). 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.

¹ Supported by a postdoctoral fellowship from the Cancer Research Institute.

² Supported by National Institutes of Health Grants AI45889 and AI49833. The recipient of a Career Scientist Award from the Hirschl Trust.

³ Supported by James Bardrick in the form of a Personal Research Chair and as a former Lister-Institute-Jenner Research Fellow, the Medical Research Council (UK) and The Wellcome Trust.

⁴ To whom correspondence should be addressed: Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 300 Cedar St., P. O. Box 208011, New Haven, CT 06520-8011. Tel.: 203-785-5176; Fax: 203-785-4461; E-mail: peter.cresswell{at}yale.edu.

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

This article has been cited by other articles:

				W. Yuan, S.-J. Kang, J. E. Evans, and P. Cresswell Natural Lipid Ligands Associated with Human CD1d Targeted to Different Subcellular Compartments J. Immunol., April 15, 2009; 182(8): 4784 - 4791. [Abstract] [Full Text] [PDF]

				W. Yuan, X. Qi, P. Tsang, S.-J. Kang, P. A. Illarionov, G. S. Besra, J. Gumperz, and P. Cresswell Saposin B is the dominant saposin that facilitates lipid binding to human CD1d molecules PNAS, March 27, 2007; 104(13): 5551 - 5556. [Abstract] [Full Text] [PDF]