NDLI: Calnexin Recognizes Carbohydrate and Protein Determinants of Class I Major Histocompatibility Complex Molecules

Content Provider	Journal of Biological Chemistry (JBC)
Author	Zhang, Qing Tector, Matthew Salter, Russell D.
Abstract	Proper folding of nascent polypeptides is essential for their function and is monitored by intracellular “quality control” elements. The molecular chaperone calnexin participates in this process by retaining in the endoplasmic reticulum a variety of unfolded proteins, including class I major histocompatibility complex molecules. We transfected human B cell lines with genes encoding either wild-type HLA-A2 heavy chains or mutant heavy chains lacking sites for glycosylation or deficient in binding to β2-microglobulin (β2m). In CIR cells, calnexin did not associate detectably with wild-type heavy chains but bound strongly to mutant heavy chains unable to bind β2m. Removal of the glycosylation addition site by further mutagenesis prevented binding of mutant heavy chains to calnexin. In Daudi cells, deficient in synthesis of β2m, wild-type HLA-A2 heavy chains, but not a nonglycosylated mutant, bound calnexin. Castanospermine, which blocks trimming of glucose residues from asparagine-linked glycans, inhibited association of calnexin with heavy chains encoded by a second class I gene, HLA-B*0702. Although initiation of calnexin binding appears to depend on the presence of oligosaccharide on the substrate, removal of the glycan from calnexin-associated heavy chains by digestion with endoglycosidase H did not disrupt the interaction. These results suggest that calnexin first recognizes carbohydrate on substrate proteins and then binds more stably to peptide determinants, which disappear upon folding.
Related Links	http://www.jbc.org/content/270/8/3944.abstract
Ending Page	3948
Starting Page	3944
Page Count	5
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	8
Volume Number	270
DOI	10.1074/jbc.270.8.3944
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	1995-02-24
Access Restriction	Open
Subject Keyword	Protein Chemistry and Structure
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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