Differences between Human and Mouse IgM Fc Receptor (FcµR).
Both non-immune "natural" and antigen-induced "immune" IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since the bona fide IgM Fc receptor (FcµR) was identified in humans by a functional cloning strategy in 2009, the roles of FcµR in these IgM effector functions have begun to be explored. In this short essay, we describe the differences between human and mouse FcµRs in terms of their identification processes, cellular distributions and ligand binding activities with emphasis on our recent findings from the mutational analysis of human FcµR. We have identified at least three sites of human FcµR, i.e., Asn66 in the CDR2, Lys79 to Arg83 in the DE loop and Asn109 in the CDR3, responsible for its constitutive IgM-ligand binding. Results of computational structural modeling analysis are consistent with these mutational data and a model of the ligand binding, Ig-like domain of human FcµR is proposed. Serendipitously, substitution of Glu41 and Met42 in the CDR1 of human FcµR with mouse equivalents Gln and Leu, either single or more prominently in combination, enhances both the receptor expression and IgM binding. These findings would help in the future development of preventive and therapeutic interventions targeting FcµR.
['Kubagawa|Hiromi|H|', 'Skopnik|Christopher M|CM|', 'Al-Qaisi|Khlowd|K|', 'Calvert|Rosaleen A|RA|', 'Honjo|Kazuhito|K|', 'Kubagawa|Yoshiki|Y|', 'Teuber|Ruth|R|', 'Aliabadi|Pedram Mahmoudi|PM|', 'Enghard|Philipp|P|', 'Radbruch|Andreas|A|', 'Sutton|Brian J|BJ|0000-0002-4363-7568']
D000818:Animals D051017:Apoptosis Regulatory Proteins D001665:Binding Sites D003001:Cloning, Molecular D006801:Humans D007075:Immunoglobulin M D008024:Ligands D008565:Membrane Proteins D051379:Mice D008958:Models, Molecular D009154:Mutation D011485:Protein Binding D011487:Protein Conformation
FcµR computational structural model IgM binding 3D structure FcR Fcα/µR pIgR species difference