title: Biogenesis and function of IgM: the role of the conserved mu-chain tailpiece glycans.
abstract: The tailpiece of secretory Ig-mu-chains (mu(s)tp) is highly conserved throughout evolution: in particular, a carboxy-terminal cysteine residue (Cys575) and a glycan linked to Asn563 are found in all species sequenced so far. Here we show that the mu(s)tp oligosaccharide moieties are important for the binding of J-chains and for the process of IgM polymerization. In the absence of the mu(s)tp glycans, pentamers cannot be assembled and polymers containing six or more subunits are secreted. Despite their increased valency, these molecules have a lower association rate with antigen than wild-type polymers. Unexpectedly, the C-terminal oligosaccharides also affect kinetic parameters on unpolymerized subunits. Thus, monomers lacking the C-terminal sugars because of either site-directed mutagenesis or selective enzymatic deglycosylation with endoglycosidase H, have a lower k(on) for the antigen. Taken together, our results indicate that the C-terminal mu-chain glycans can shape the structure of mu(s2)L2 subunits and their further assembly into polymers.
authors.affiliation: DIBIT, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: de Lalla
authors.forename: C
authors.initials: C
authors.lastname: Fagioli
authors.forename: F S
authors.initials: FS
authors.lastname: Cessi
authors.forename: D
authors.initials: D
authors.lastname: Smilovich
authors.forename: R
authors.initials: R
authors.lastname: Sitia
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006031:Glycosylation; D006461:Hemolysis; D007075:Immunoglobulin M / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D007148:Immunoglobulin mu-Chains / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D016297:Mutagenesis, Site-Directed; D011134:Polysaccharides / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D011134:Polysaccharides