title: Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor.
abstract: IgM is the first antibody to be produced in immune responses and plays an important role in the neutralization of bacteria and viruses. Human IgM is heavily glycosylated, featuring five N-linked glycan sites on the μ chain and one on the J-chain. Glycosylation of IgG is known to modulate the effector functions of Fcγ receptors. In contrast, little is known about the effect of glycosylation on IgM binding to the human Fcμ receptor (hFCMR). In this study, we identify the Cμ4 domain of IgM as the target of hFCMR, and show that binding and internalization of IgM by hFCMR is glycan-independent. We generated a homology-based structure for hFCMR and used molecular dynamic simulations to show how this interaction with IgM may occur. Finally, we reveal an inhibitory function for IgM in the proliferation of T cells.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: Katy A
authors.initials: KA
authors.lastname: Lloyd
authors.affiliation: Key Laboratory of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: Britta C
authors.initials: BC
authors.lastname: Urban
authors.affiliation: Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Czajkowsky
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pleass
mesh_terms: D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D004705:Endocytosis; D006031:Glycosylation; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D056004:Molecular Dynamics Simulation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D007075:Immunoglobulin M; D010835:Phytohemagglutinins; D011134:Polysaccharides; D011961:Receptors, Fc