Ubiquitination and dimerization of complement receptor type 2 on sheep B cells.
Complement receptor type 2 (CR2) is a membrane-anchored glycoprotein that specifically binds C3d, as well as other ligands, and plays diverse roles in regulating immunity. Here we show that two distinct isoforms of CR2 are expressed on the surface of sheep B lymphocytes. One (CR2no 150 kDa) is structurally similar to known mammalian homologues while the other (CR2ub 190 kDa) has been modified by the covalent attachment of ubiquitin to the cytoplasmic domain and is identified for the first time. CR2no and CR2ub are expressed on the surface of sheep B cells as noncovalently associated dimers and the external topography of the two isoforms differs in some respect. The basis for these unusual higher-order structural properties may lie in the primary sequence of sheep CR2, since the transmembrane domain contains a region resembling a rare 7-amino acid dimerization motif, and two lysine residues in the cytoplasmic domain provide potential sites for posttranslational ubiquitination. The primary structures of sheep ubiquitin and C3d ligand are extensively conserved. In conjunction with the results of separate in vivo studies, these findings suggest that selective ubiquitination plays a role in modulating the higher-order structure and/or expression of CR2 during B cell development.
Hein
W R
WR
Basel Institute for Immunology, Switzerland.
Dudler
L
L
Marston
W L
WL
Landsverk
T
T
Young
A J
AJ
Avila
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody; D001704:Biopolymers / Q000378:metabolism; D015933:Complement C3d / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D003593:Cytoplasm / Q000737:chemistry; D019281:Dimerization; D005110:Extracellular Space / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D025821:Polyubiquitin; D017434:Protein Structure, Tertiary; D017464:Receptors, Complement 3d / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D012756:Sheep / Q000276:immunology*; D014452:Ubiquitins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001704:Biopolymers; D008024:Ligands; D008565:Membrane Proteins; D017464:Receptors, Complement 3d; D014452:Ubiquitins; D025821:Polyubiquitin; D015933:Complement C3d