Origin of bovine IgM structural variants.
The structure of IgM determined from two cDNAs isolated from a Holstein (BLV7G1) and an Angus x Hereford cross-bred (B5D8) cow reveals high sequence similarity both at nucleotide (98.7%) and amino acid (97.9%) level and is closest to sheep (89.4%). Three bovine IgM allotypes, designated as IgMa, IgMb and IgMc, are classified based on nucleotide substitutions in all the Cmu exons resulting in amino acid replacements. Further, insertion of three in-frame codons at Cmu1 and Cmu2 junction of B5D8 IgM from the intervening intron, via cleavage of pre-mRNA at an alternate cryptic 5' splice donor site, leads to generation of additional bovine IgM variants. The C1q-binding site, involved in classical complement pathway, is identified in bovine IgM where ten amino acids are conserved across species. Interestingly, bovine IgM has the lowest number of proline residues (5) in the Cmu2 domain in comparison to other species (7-9) and this is likely to impose structural constraints on mobility of Fab arms of the bovine IgM during antigen recognition. The rigidity in the bovine IgM Cmu2 domain may, however, facilitate exposure of C1q-binding site subsequent to antigen binding and enhance its complement fixing ability. The restricted mobility of bovine IgM Fab arms may possibly favor generation of an antigen-combining site requiring an unusually long third complementarity determining region of the heavy chain (CDR3H), apart from antigen selection of variable domains. This is consistent with the fact that an exceptionally long CDR3H has not been observed in bovine IgG which bears a long and more flexible hinge region. Additional hydrophilic threonine and serine residues in the Cmu2 domain of bovine IgM, as compared to other species, however, enhance its ability to extend into the solvent. Finally, restricted fragment length polymorphism analysis of genomic DNA from four cattle breeds reveals the presence of; at least, four allelic variants of bovine Cmu gene.
Saini
S S
SS
Department of Pathobiology, University of Guelph, Ont., N1G 2W1, Guelph, Canada.
Kaushik
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D018076:DNA, Complementary; D014644:Genetic Variation; D007126:Immunoglobulin Allotypes; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics* / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D022821:RNA Splice Sites
D018076:DNA, Complementary; D007126:Immunoglobulin Allotypes; D007127:Immunoglobulin Constant Regions; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D022821:RNA Splice Sites