title: Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking.
abstract: CD22 is a negative regulator of B-cell receptor signaling, an activity mediated by recruitment of SH2 domain-containing phosphatase 1 through a phosphorylated immunoreceptor tyrosine inhibitory motif in its cytoplasmic domain. As in other members of the sialic acid-binding immunoglobulin-like lectin, or siglec, family, the extracellular N-terminal immunoglobulin domain of CD22 binds to glycan ligands containing sialic acid, which are highly expressed on B-cell glycoproteins. B-cell glycoproteins bind to CD22 in cis and 'mask' the ligand-binding domain, modulating its activity as a regulator of B-cell signaling. To assess cell-surface cis ligand interactions, we developed a new method for in situ photoaffinity cross-linking of glycan ligands to CD22. Notably, CD45, surfaceIgM (sIgM) and other glycoproteins that bind to CD22 in vitro do not appear to be important cis ligands of CD22 in situ. Instead, CD22 seems to recognize glycans of neighboring CD22 molecules as cis ligands, forming homomultimeric complexes.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, MEM-L71, La Jolla, California 92037, USA.
authors.forename: Shoufa
authors.initials: S
authors.lastname: Han
authors.forename: Brian E
authors.initials: BE
authors.lastname: Collins
authors.forename: Per
authors.initials: P
authors.lastname: Bengtson
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
mesh_terms: D001386:Azides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001386:Azides; D011134:Polysaccharides; D051918:Sialic Acid Binding Ig-like Lectin 2; D019158:N-Acetylneuraminic Acid